Graft-versus-host disease was studied on the 10th and 14th postoperative days in Lewis x Brown Norway F1rats (LBN-F1) receiving Lewis accessory heterotopic intestinal allografts. LBN-F1isograft recipients and LBN-F1rats were used as controls. The rats were injected with sheep erythrocytes five days before sacrifice.Rats with graft-versus-host disease had progressive loss of the normal architecture of the lymphoid organs. Skin, liver, colon, and salivary glands were infiltrated with immunoblasts and had patchy areas of necrosis. Concurrent with these changes, there were significant, progressive reductions in hemolytic titers, splenocyte plaque-forming counts, viable splenocytes, and the invitro splenocyte response to stimulation with concanavalin A.Graft-versus-host disease following intestinal allotransplantation damages the host's lymphoid tissues, producing profound immunosuppression. This finding has implications for clinical intestinal transplantation.