Two immunosuppressive regimens-cyclosporine plus prednisone and azathioprine plus prednisone-were compared in 78 renal transplantation patients (39 in each treatment group) who were successfully managed for more than 15 months. In patients who received cyclosporine, the dosage was adjusted to achieve trough whole blood concentrations of 100 to 250 ng/ml measured by liquid chromatography. A greater number of haplotypes matched in the azathioprine-treated group than in the cyclosporine-treated group (P less than 0.026). Graft survival was similar in patients who received azathioprine (95%) and those given cyclosporine (94%). The azathioprine group had a higher mortality (7%) than the cyclosporine group (2%). In a comparison of the two treatment groups, no statistically significant difference was found in posttransplant renal function, based on either serum creatinine or iothalamate clearance. We conclude that renal toxicity due to cyclosporine can be minimized to statistical nonsignificance by using cyclosporine dosages that provide trough whole blood concentrations in the range of 150 to 250 ng/ml during the first 4 months of therapy and 80 to 200 ng/ml thereafter.