The hypothesis tested in the present and accompanying study is that and effective treatment for severe burns involves early excision of necrotic tissute followed by skin allografting ad cylosporine (CsA) immunosuppressive therapy. LEW (RR11) rats served as recipients of thermal injury and/or skin allografts. BNxLEW F1M(LBN, RT11+n) rats served as skin donors. LEW burn recipients received a hot water (90oC for 10 sec) 30% body surface area (BSA) full-thickness burn. As expected, LEW recipients treated with CsA (25 mg/kg/day for 20 days) demonstrated singnificant graft polongation compared with controls (P<0.005). Skin graft survival was similarly prolonged in LEW recipeints undergoing burn unjury, primary wound excision, and CsA administration comkpared with not increased in the thermal injury—CsA-treated recipients comkpared with burn controls. A final experiment was initiated to investigate how low-level long-term (>100 days) maintenace CsA treatment influenced skin allograft survivalfor possible future consideration in burn trauma. Recipioents receiving skin allografts plus CsA (20 days, 8mg/kg/day, followed by every other day therafter) did not reject their grafts. However, a possible early sign of rejection ( a gingle small ulceratiove lesion) was noted in five of these long-term CsA-treated animals at a meanof 3411 (SD) days. The lesion in these animals did not progress any further during CsA administration. His-topathologic study of selected animals removed from the CsA maintenance regimen for greter than 50 days following long-term administration revealed a number of interesting chronic lesions similar to thosse previously reported in the skin comonent of composite tissue (limb) allografts following long-term low-level CsA intervention. In conclusion, CsA was very successful in preventing rejection of skin allografts in a rat burn model without apparent adverse effects.