diff --git a/openslide/lowlevel.py b/openslide/lowlevel.py
index 6c6f95e5..91f7eb07 100644
--- a/openslide/lowlevel.py
+++ b/openslide/lowlevel.py
@@ -29,6 +29,7 @@
 rather than in the high-level interface.)
 """
 
+from __future__ import division
 from ctypes import *
 from itertools import count
 import PIL.Image
@@ -63,16 +64,49 @@ def _load_image(buf, size):
         return PIL.Image.frombuffer('RGBA', size, buf, 'raw', 'RGBA', 0, 1)
 except ImportError:
     def _load_image(buf, size):
-        '''buf can be a string, but should be a ctypes buffer to avoid an
-        extra copy in the caller.'''
-        # First reorder the bytes in a pixel from native-endian aRGB to
-        # big-endian RGBa to work around limitations in RGBa loader
-        rawmode = (sys.byteorder == 'little') and 'BGRA' or 'ARGB'
-        buf = PIL.Image.frombuffer('RGBA', size, buf, 'raw', rawmode, 0, 1)
-        # Image.tobytes() is named tostring() in Pillow 1.x and PIL
-        buf = (getattr(buf, 'tobytes', None) or buf.tostring)()
-        # Now load the image as RGBA, undoing premultiplication
-        return PIL.Image.frombuffer('RGBA', size, buf, 'raw', 'RGBa', 0, 1)
+        '''buf must be a buffer.'''
+
+        # Load entire buffer at once if possible
+        MAX_PIXELS_PER_LOAD = (1 << 29) - 1
+        # Otherwise, use chunks smaller than the maximum to reduce memory
+        # requirements
+        PIXELS_PER_LOAD = 1 << 26
+
+        def do_load(buf, size):
+            '''buf can be a string, but should be a ctypes buffer to avoid an
+            extra copy in the caller.'''
+            # First reorder the bytes in a pixel from native-endian aRGB to
+            # big-endian RGBa to work around limitations in RGBa loader
+            rawmode = (sys.byteorder == 'little') and 'BGRA' or 'ARGB'
+            buf = PIL.Image.frombuffer('RGBA', size, buf, 'raw', rawmode, 0, 1)
+            # Image.tobytes() is named tostring() in Pillow 1.x and PIL
+            buf = (getattr(buf, 'tobytes', None) or buf.tostring)()
+            # Now load the image as RGBA, undoing premultiplication
+            return PIL.Image.frombuffer('RGBA', size, buf, 'raw', 'RGBa', 0, 1)
+
+        # Fast path for small buffers
+        w, h = size
+        if w * h <= MAX_PIXELS_PER_LOAD:
+            return do_load(buf, size)
+
+        # Load in chunks to avoid OverflowError in PIL.Image.frombuffer()
+        # https://github.com/python-pillow/Pillow/issues/1475
+        if w > PIXELS_PER_LOAD:
+            # We could support this, but it seems like overkill
+            raise ValueError('Width %d is too large (maximum %d)' %
+                    (w, PIXELS_PER_LOAD))
+        rows_per_load = PIXELS_PER_LOAD // w
+        img = PIL.Image.new('RGBA', (w, h))
+        for y in range(0, h, rows_per_load):
+            rows = min(h - y, rows_per_load)
+            if sys.version[0] == '2':
+                chunk = buffer(buf, 4 * y * w, 4 * rows * w)
+            else:
+                # PIL.Image.frombuffer() won't take a memoryview or
+                # bytearray, so we can't avoid copying
+                chunk = memoryview(buf)[y * w:(y + rows) * w].tobytes()
+            img.paste(do_load(chunk, (w, rows)), (0, y))
+        return img
 
 class OpenSlideError(Exception):
     """An error produced by the OpenSlide library.
diff --git a/tests/test_openslide.py b/tests/test_openslide.py
index ef0b317c..e8c329a3 100644
--- a/tests/test_openslide.py
+++ b/tests/test_openslide.py
@@ -120,6 +120,20 @@ def test_read_region_bad_size(self):
         self.assertRaises(OpenSlideError,
                 lambda: self.osr.read_region((0, 0), 1, (400, -5)))
 
+    def test_read_region_2GB(self):
+        self.assertEqual(
+                self.osr.read_region((1000, 1000), 0, (32768, 16384)).size,
+                (32768, 16384))
+
+    def test_read_region_2GB_width(self):
+        try:
+            import openslide._convert
+            return
+        except ImportError:
+            pass
+        self.assertRaises(ValueError,
+                lambda: self.osr.read_region((1000, 1000), 0, (1 << 29, 1)))
+
     def test_thumbnail(self):
         self.assertEqual(self.osr.get_thumbnail((100, 100)).size, (100, 83))