Sixty rat hind-limb allotransplantations across strong histocompatibility barriers were performed. Group I (isograft controls), (Lewis-Brown-Norway [LBN] to LBN) limb transplantations were performed; Group II (rejection controls), LBN limbs transplanted to Lewis rat LEW recipients with no immunosuppressive treatment; Group III (steroid group), fluocinolone acetonide (50 pg/ml) was applied topically; Group IV (cyclosporine group), 4 mg/kg of cyclosporine was administered subcutaneously daily; Group V (combination group), combined systemic cyclosporine with topical fluocinolone acetonide was administered daily. Group II: Limb rejection was present on the fourth day. Group III: Limb survival was extended for 3 weeks with no signs of skin rejection in 75% of animals. Group IV: Rejection was complete at 3 weeks. Group V: Limbs survived to 6 weeks. Topical steroid prevented skin rejection and delayed rejection of other components of the composite allograft. Combined treatment of topical steroid and low cyclosporine doses significantly extended survival rate of limb allografts.