Delayed administration of bortezomib significantly increases gut histopathologic damage in mice with GVHD. B6 (H2^b) recipients of BALB/c (H2^d) 10 million bone marrow and 15 million spleen cells were treated with or without 15 μg bortezomib per dose daily on day 12 after BMT. The next day (day 13) mice were humanely killed and gut tissue was collected, processed, and stained with hematoxylin and eosin. (A-C) Small intestine from mice without delayed bortezomib treatment (A) have hyperplastic crypts (c) but normal villi (v). In contrast, the small intestines from mice with delayed bortezomib treatment (B-C) have villous blunting and fusion (v), hyperplastic crypts (c), and an inflammatory infiltrate (arrow). Other areas of small intestine are ulcerated (u) with a base of inflammatory cells. (D-F) Colons from mice without delayed bortezomib treatment (D) display relatively normal morphology. In contrast, colons from mice with delayed bortezomib treatment have increased (E) goblet cell depletion and inflammatory cells (arrow) in the lamina propria. Other areas of colon (F) are ulcerated (u), have sloughed cells in crypt lumens (c), and inflammation in the ulcer base and the submucosa (Sm). Original magnification × 200.