The effects of cyclosporine (CsA) on renal function and morphology have been studied in the rat after unilateral nephrectomy and warm renal ischemia. There is evidence of an enhanced CsA nephrotoxic effect after unilateral nephrectomy alone and of an additive or synergistic effect of CsA and renal ischemia upon renal function and morphology. These enhanced effects are most evident after longer periods of ischemia (60 min) and with higher doses of CsA (25 mg/kg/day). The findings may be relevant to clinical practice and suggest that the nephrotoxic effects of CsA upon the donor kidney may be greatest when there is coincident renal damage from other causes.