Attenuation of GVHD severity is attributable to the preferential reduction of pathologic damage in the colon. Lethally irradiated Balb/c (900 cGy) (A) or FVB (1000 cGy) (B) mice were transplanted with B6 BM (10 × 10⁶) plus spleen cells (■) or IL-23^−/− BM (10 × 10⁶) and spleen cells (□) adjusted to yield an equivalent number of mature T cells. Mice were killed 20 to 29 days after transplantation, and GVHD target tissues (colon, liver, and lung) were examined for pathologic damage using a semiquantitative scoring system as detailed in “Histologic analysis.” Data are presented as the mean (± SEM) and are the cumulative results from 3 (n = 14-15/group for Balb/c) or 4 (n = 16-19 for FVB) experiments. **P < .01. (C-H) Histology of colon (C,F), liver (D,G), and lung (E,H) from representative FVB recipients 20 to 29 days after transplantation with B6 BM and spleen cells (C-E) or IL-23 BM and spleen cells (F-H). Colon in panel C shows ulceration of the mucosal surface, extensive crypt cell destruction, and goblet cell depletion, while colon in panel F has normal appearing mucosa with no inflammatory infiltration and preserved goblet cell content. Livers in panels D and G both show infiltration in the portal triads with mononuclear and granulocytic cells (p), endothelialitis and hepatocellular apoptosis (arrows). Lungs in panels E and H demonstrate peribronchial (b) and perivascular (v) cuffing attributable to mononuclear and granulocytic cells along with associated interstitial inflammation.