This study was done to define the tolerance of ex vivo administered irradiation to intestinal allograft and to assess the effect of irradiation on the incidence and severity of rejection and graft versus host disease after intestinal transplantation in dogs. Excessive intestinal damage was produced by 2,500 rads, but 750 and 1,500 rads produced no detectable acute or chronic damage in dogs observed from 100 days to two years. Using cyclosporine for postoperative immunosuppression, 1,500 rads reduced the incidence of acute (p = 0.05) and chronic rejection (p = 0.08), yet did not impair intestinal absorption of cyclosporine. The greatest improvement in survival occurred with 750 rads (p = 0.02). Histologic evidence of graft versus host disease appeared in the native small intestine in two of four long term surviving dogs receiving a nonirradiated graft but in none of the dogs receiving irradiated grafts. Irradiation of the graft may be a promising adjunct in the search for a clinically applicable method of intestinal transplantation.