We compared CsG and CsA in the DA-to-Lewis rat renal allograft model. At equivalent oral doses, plasma radioimmunoassay (RIA) CsG levels were higher than CsA (P less than 0.02). Neither drug prevented rejection at doses of 5 mg/kg/day. CsG-treated rats had a higher rejection rate at doses of 7.5 mg/kg/day (P less than 0.05). Both drugs were equally effective in preventing rejection at doses of 10 mg/kg/day. Neither drug was nephrotoxic at the doses used in this study. CsG is a potent immunosuppressant, and thus a potential clinical successor to CsA. Since CsG and CsA provide equivalent immunosuppression at therapeutic doses, CsG's clinical significance will ultimately depend on its nephrotoxicity in man.