The immunosuppressive effect of combined therapy using FK-506 and 15-deoxyspergualin was investigated in rat limb allotransplantation. The right hindlimb of an inbred Dark Agouti rat (RT1a) was transplanted to a Lewis rat (RT1l) and observed for 120 days. Eighty-eight transplantations were performed. Rejection of the grafts was evaluated histologically as well as macroscopically. A pathologic grading system was used to rate the severity of rejection. Limb survival time in Lewis rats receiving FK-506 therapy for days was significantly prolonged by combined therapy with 15-deoxyspergualin. Histologic study showed practically no rejection in all the graft-composing tissues except the skin and bone marrow, in which there was rejection. These results suggest that tissues like bone, cartilage, and muscle may survive transplantation with short-term combination FK-506 and 15-deoxyspergualin therapy even after withdrawal of both agents.