diff --git a/cpu-exec.c b/cpu-exec.c
index 1613c63..e1fb9ca 100644
--- a/cpu-exec.c
+++ b/cpu-exec.c
@@ -29,6 +29,7 @@
 #include "qemu/rcu.h"
 #include "exec/tb-hash.h"
 #include "exec/log.h"
+#include "qemu/main-loop.h"
 #if defined(TARGET_I386) && !defined(CONFIG_USER_ONLY)
 #include "hw/i386/apic.h"
 #endif
@@ -460,6 +461,8 @@ static inline void cpu_handle_interrupt(CPUState *cpu,
     int interrupt_request = cpu->interrupt_request;
 
     if (unlikely(interrupt_request)) {
+        qemu_mutex_lock_iothread();
+
         if (unlikely(cpu->singlestep_enabled & SSTEP_NOIRQ)) {
             /* Mask out external interrupts for this step. */
             interrupt_request &= ~CPU_INTERRUPT_SSTEP_MASK;
@@ -514,6 +517,10 @@ static inline void cpu_handle_interrupt(CPUState *cpu,
                the program flow was changed */
             *last_tb = NULL;
         }
+
+        /* If we exit via cpu_loop_exit/longjmp it is reset in cpu_exec */
+        qemu_mutex_unlock_iothread();
+
     }
     if (unlikely(cpu->exit_request || replay_has_interrupt())) {
         cpu->exit_request = 0;
@@ -642,8 +649,12 @@ int cpu_exec(CPUState *cpu)
             g_assert(cpu == current_cpu);
             g_assert(cc == CPU_GET_CLASS(cpu));
 #endif /* buggy compiler */
+
             cpu->can_do_io = 1;
             tb_lock_reset();
+            if (qemu_mutex_iothread_locked()) {
+                qemu_mutex_unlock_iothread();
+            }
         }
     } /* for(;;) */
 
diff --git a/cpus.c b/cpus.c
index a84f02c..35374fd 100644
--- a/cpus.c
+++ b/cpus.c
@@ -915,8 +915,6 @@ static void qemu_kvm_init_cpu_signals(CPUState *cpu)
 #endif /* _WIN32 */
 
 static QemuMutex qemu_global_mutex;
-static QemuCond qemu_io_proceeded_cond;
-static unsigned iothread_requesting_mutex;
 
 static QemuThread io_thread;
 
@@ -932,7 +930,6 @@ void qemu_init_cpu_loop(void)
     qemu_cond_init(&qemu_cpu_cond);
     qemu_cond_init(&qemu_pause_cond);
     qemu_cond_init(&qemu_work_cond);
-    qemu_cond_init(&qemu_io_proceeded_cond);
     qemu_mutex_init(&qemu_global_mutex);
 
     qemu_thread_get_self(&io_thread);
@@ -1045,10 +1042,6 @@ static void qemu_tcg_wait_io_event(CPUState *cpu)
         qemu_cond_wait(cpu->halt_cond, &qemu_global_mutex);
     }
 
-    while (iothread_requesting_mutex) {
-        qemu_cond_wait(&qemu_io_proceeded_cond, &qemu_global_mutex);
-    }
-
     CPU_FOREACH(cpu) {
         qemu_wait_io_event_common(cpu);
     }
@@ -1205,7 +1198,9 @@ static int tcg_cpu_exec(CPUState *cpu)
         cpu->icount_decr.u16.low = decr;
         cpu->icount_extra = count;
     }
+    qemu_mutex_unlock_iothread();
     ret = cpu_exec(cpu);
+    qemu_mutex_lock_iothread();
 #ifdef CONFIG_PROFILER
     tcg_time += profile_getclock() - ti;
 #endif
@@ -1392,22 +1387,7 @@ bool qemu_mutex_iothread_locked(void)
 
 void qemu_mutex_lock_iothread(void)
 {
-    atomic_inc(&iothread_requesting_mutex);
-    /* In the simple case there is no need to bump the VCPU thread out of
-     * TCG code execution.
-     */
-    if (!tcg_enabled() || qemu_in_vcpu_thread() ||
-        !first_cpu || !first_cpu->created) {
-        qemu_mutex_lock(&qemu_global_mutex);
-        atomic_dec(&iothread_requesting_mutex);
-    } else {
-        if (qemu_mutex_trylock(&qemu_global_mutex)) {
-            qemu_cpu_kick_rr_cpu();
-            qemu_mutex_lock(&qemu_global_mutex);
-        }
-        atomic_dec(&iothread_requesting_mutex);
-        qemu_cond_broadcast(&qemu_io_proceeded_cond);
-    }
+    qemu_mutex_lock(&qemu_global_mutex);
     iothread_locked = true;
 }
 
diff --git a/cputlb.c b/cputlb.c
index 1ff6354..78e9879 100644
--- a/cputlb.c
+++ b/cputlb.c
@@ -18,6 +18,7 @@
  */
 
 #include "qemu/osdep.h"
+#include "qemu/main-loop.h"
 #include "cpu.h"
 #include "exec/exec-all.h"
 #include "exec/memory.h"
diff --git a/exec.c b/exec.c
index e23039c..b7744b9 100644
--- a/exec.c
+++ b/exec.c
@@ -2149,9 +2149,9 @@ static void check_watchpoint(int offset, int len, MemTxAttrs attrs, int flags)
                 }
                 cpu->watchpoint_hit = wp;
 
-                /* The tb_lock will be reset when cpu_loop_exit or
-                 * cpu_resume_from_signal longjmp back into the cpu_exec
-                 * main loop.
+                /* Both tb_lock and iothread_mutex will be reset when
+                 * cpu_loop_exit or cpu_resume_from_signal longjmp
+                 * back into the cpu_exec main loop.
                  */
                 tb_lock();
                 tb_check_watchpoint(cpu);
@@ -2387,8 +2387,14 @@ static void io_mem_init(void)
     memory_region_init_io(&io_mem_rom, NULL, &unassigned_mem_ops, NULL, NULL, UINT64_MAX);
     memory_region_init_io(&io_mem_unassigned, NULL, &unassigned_mem_ops, NULL,
                           NULL, UINT64_MAX);
+
+    /* io_mem_notdirty calls tb_invalidate_phys_page_fast,
+     * which must be called without the iothread mutex.
+     */
     memory_region_init_io(&io_mem_notdirty, NULL, &notdirty_mem_ops, NULL,
                           NULL, UINT64_MAX);
+    memory_region_clear_global_locking(&io_mem_notdirty);
+
     memory_region_init_io(&io_mem_watch, NULL, &watch_mem_ops, NULL,
                           NULL, UINT64_MAX);
 }
diff --git a/hw/i386/kvmvapic.c b/hw/i386/kvmvapic.c
index d98fe2a..12ed58e 100644
--- a/hw/i386/kvmvapic.c
+++ b/hw/i386/kvmvapic.c
@@ -450,8 +450,8 @@ static void patch_instruction(VAPICROMState *s, X86CPU *cpu, target_ulong ip)
     resume_all_vcpus();
 
     if (!kvm_enabled()) {
-        /* tb_lock will be reset when cpu_resume_from_signal longjmps
-         * back into the cpu_exec loop. */
+        /* Both tb_lock and iothread_mutex will be reset when
+         * cpu_resume_from_signal longjmps back into the cpu_exec loop. */
         tb_lock();
         tb_gen_code(cs, current_pc, current_cs_base, current_flags, 1);
         cpu_resume_from_signal(cs, NULL);
diff --git a/memory.c b/memory.c
index 4e3cda8..2a318d7 100644
--- a/memory.c
+++ b/memory.c
@@ -914,6 +914,8 @@ void memory_region_transaction_commit(void)
     AddressSpace *as;
 
     assert(memory_region_transaction_depth);
+    assert(qemu_mutex_iothread_locked());
+
     --memory_region_transaction_depth;
     if (!memory_region_transaction_depth) {
         if (memory_region_update_pending) {
diff --git a/softmmu_template.h b/softmmu_template.h
index 208f808..0b6c609 100644
--- a/softmmu_template.h
+++ b/softmmu_template.h
@@ -151,6 +151,7 @@ static inline DATA_TYPE glue(io_read, SUFFIX)(CPUArchState *env,
     CPUState *cpu = ENV_GET_CPU(env);
     hwaddr physaddr = iotlbentry->addr;
     MemoryRegion *mr = iotlb_to_region(cpu, physaddr, iotlbentry->attrs);
+    bool locked = false;
 
     physaddr = (physaddr & TARGET_PAGE_MASK) + addr;
     cpu->mem_io_pc = retaddr;
@@ -159,8 +160,15 @@ static inline DATA_TYPE glue(io_read, SUFFIX)(CPUArchState *env,
     }
 
     cpu->mem_io_vaddr = addr;
+    if (mr->global_locking) {
+        qemu_mutex_lock_iothread();
+        locked = true;
+    }
     memory_region_dispatch_read(mr, physaddr, &val, 1 << SHIFT,
                                 iotlbentry->attrs);
+    if (locked) {
+        qemu_mutex_unlock_iothread();
+    }
     return val;
 }
 #endif
@@ -358,6 +366,7 @@ static inline void glue(io_write, SUFFIX)(CPUArchState *env,
     CPUState *cpu = ENV_GET_CPU(env);
     hwaddr physaddr = iotlbentry->addr;
     MemoryRegion *mr = iotlb_to_region(cpu, physaddr, iotlbentry->attrs);
+    bool locked = false;
 
     physaddr = (physaddr & TARGET_PAGE_MASK) + addr;
     if (mr != &io_mem_rom && mr != &io_mem_notdirty && !cpu->can_do_io) {
@@ -366,8 +375,16 @@ static inline void glue(io_write, SUFFIX)(CPUArchState *env,
 
     cpu->mem_io_vaddr = addr;
     cpu->mem_io_pc = retaddr;
+
+    if (mr->global_locking) {
+        qemu_mutex_lock_iothread();
+        locked = true;
+    }
     memory_region_dispatch_write(mr, physaddr, val, 1 << SHIFT,
                                  iotlbentry->attrs);
+    if (locked) {
+        qemu_mutex_unlock_iothread();
+    }
 }
 
 void helper_le_st_name(CPUArchState *env, target_ulong addr, DATA_TYPE val,
diff --git a/target-i386/smm_helper.c b/target-i386/smm_helper.c
index 4dd6a2c..6a5489b 100644
--- a/target-i386/smm_helper.c
+++ b/target-i386/smm_helper.c
@@ -18,6 +18,7 @@
  */
 
 #include "qemu/osdep.h"
+#include "qemu/main-loop.h"
 #include "cpu.h"
 #include "exec/helper-proto.h"
 #include "exec/log.h"
@@ -42,11 +43,14 @@ void helper_rsm(CPUX86State *env)
 #define SMM_REVISION_ID 0x00020000
 #endif
 
+/* Called we iothread lock taken */
 void cpu_smm_update(X86CPU *cpu)
 {
     CPUX86State *env = &cpu->env;
     bool smm_enabled = (env->hflags & HF_SMM_MASK);
 
+    g_assert(qemu_mutex_iothread_locked());
+
     if (cpu->smram) {
         memory_region_set_enabled(cpu->smram, smm_enabled);
     }
@@ -333,7 +337,10 @@ void helper_rsm(CPUX86State *env)
     }
     env->hflags2 &= ~HF2_SMM_INSIDE_NMI_MASK;
     env->hflags &= ~HF_SMM_MASK;
+
+    qemu_mutex_lock_iothread();
     cpu_smm_update(cpu);
+    qemu_mutex_unlock_iothread();
 
     qemu_log_mask(CPU_LOG_INT, "SMM: after RSM\n");
     log_cpu_state_mask(CPU_LOG_INT, CPU(cpu), CPU_DUMP_CCOP);
diff --git a/translate-all.c b/translate-all.c
index f54ab3e..818520e 100644
--- a/translate-all.c
+++ b/translate-all.c
@@ -1476,7 +1476,9 @@ void tb_invalidate_phys_page_range(tb_page_addr_t start, tb_page_addr_t end,
 }
 
 #ifdef CONFIG_SOFTMMU
-/* len must be <= 8 and start must be a multiple of len */
+/* len must be <= 8 and start must be a multiple of len.
+ * Called via softmmu_template.h, with iothread mutex not held.
+ */
 void tb_invalidate_phys_page_fast(tb_page_addr_t start, int len)
 {
     PageDesc *p;
@@ -1670,7 +1672,10 @@ void tb_check_watchpoint(CPUState *cpu)
 
 #ifndef CONFIG_USER_ONLY
 /* in deterministic execution mode, instructions doing device I/Os
-   must be at the end of the TB */
+ * must be at the end of the TB.
+ *
+ * Called by softmmu_template.h, with iothread mutex not held.
+ */
 void cpu_io_recompile(CPUState *cpu, uintptr_t retaddr)
 {
 #if defined(TARGET_MIPS) || defined(TARGET_SH4)
