The intestinal phase of the graft-versus-host reaction (GVHR) has been investigated in adult F1 mice bearing grafts of fetal gut using an H-2-incompatible and an H-2-compatible, Mls-incompatible combination. The results indicate that the mitotic activity of the intestinal crypts and the number of intraepithelial lymphocytes are sensitive parameters of the mucosal cell-mediated immune response in the GVHR. Using these indices, indirect evidence has been obtained that soluble factors may be responsible for the damage to the intestine in the GVHR. Possible pathways of lymphocyte activation and migration to the gut are proposed to explain the role of gut-associated T cells in the production of these mediators.