diff --git a/neovim/api/nvim.py b/neovim/api/nvim.py
index c405554b..b966b006 100644
--- a/neovim/api/nvim.py
+++ b/neovim/api/nvim.py
@@ -1,6 +1,7 @@
 """Main Nvim interface."""
 import os
 import sys
+import threading
 from functools import partial
 from traceback import format_stack
 
@@ -165,6 +166,15 @@ def request(self, name, *args, **kwargs):
         present and True, a asynchronous notification is sent instead. This
         will never block, and the return value or error is ignored.
         """
+        if (self._session._loop_thread is not None and
+                threading.current_thread() != self._session._loop_thread):
+
+            msg = ("request from non-main thread:\n{}\n"
+                   .format('\n'.join(format_stack(None, 5)[:-1])))
+
+            self.async_call(self._err_cb, msg)
+            raise NvimError("request from non-main thread")
+
         decode = kwargs.pop('decode', self._decode)
         args = walk(self._to_nvim, args)
         res = self._session.request(name, *args, **kwargs)
@@ -382,8 +392,18 @@ def out_write(self, msg, **kwargs):
 
     def err_write(self, msg, **kwargs):
         """Print `msg` as an error message."""
+        if self._thread_invalid():
+            # special case: if a non-main thread writes to stderr
+            # i.e. due to an uncaught exception, pass it through
+            # without raising an additional exception.
+            self.async_call(self.err_write, msg, **kwargs)
+            return
         return self.request('nvim_err_write', msg, **kwargs)
 
+    def _thread_invalid(self):
+        return (self._session._loop_thread is not None and
+                threading.current_thread() != self._session._loop_thread)
+
     def quit(self, quit_command='qa!'):
         """Send a quit command to Nvim.
 
diff --git a/neovim/msgpack_rpc/session.py b/neovim/msgpack_rpc/session.py
index b300f8d2..604d4229 100644
--- a/neovim/msgpack_rpc/session.py
+++ b/neovim/msgpack_rpc/session.py
@@ -1,5 +1,6 @@
 """Synchronous msgpack-rpc session layer."""
 import logging
+import threading
 from collections import deque
 from traceback import format_exc
 
@@ -29,6 +30,7 @@ def __init__(self, async_session):
         self._is_running = False
         self._setup_exception = None
         self.loop = async_session.loop
+        self._loop_thread = None
 
     def threadsafe_call(self, fn, *args, **kwargs):
         """Wrapper around `AsyncSession.threadsafe_call`."""
@@ -110,6 +112,7 @@ def run(self, request_cb, notification_cb, setup_cb=None):
         self._notification_cb = notification_cb
         self._is_running = True
         self._setup_exception = None
+        self._loop_thread = threading.current_thread()
 
         def on_setup():
             try:
@@ -135,6 +138,7 @@ def on_setup():
         self._is_running = False
         self._request_cb = None
         self._notification_cb = None
+        self._loop_thread = None
 
         if self._setup_exception:
             raise self._setup_exception
diff --git a/neovim/plugin/script_host.py b/neovim/plugin/script_host.py
index 97acbff4..571f47cc 100644
--- a/neovim/plugin/script_host.py
+++ b/neovim/plugin/script_host.py
@@ -208,6 +208,8 @@ def eval(self, expr):
 # This was copied/adapted from nvim-python help
 def path_hook(nvim):
     def _get_paths():
+        if nvim._thread_invalid():
+            return []
         return discover_runtime_directories(nvim)
 
     def _find_module(fullname, oldtail, path):