The safety of conversion from cyclosporine to azathioprine following renal transplantation in patients generally considered to be at immunologic risk for allograft loss has not been established. We examined a group of 59 patients who underwent cadaveric renal transplantation and elective conversion from cyclosporine to azathioprine 8.3 +/- 3.8 months following transplantation. Forty-three of these patients received a first transplant and had panel-reactive antibodies (PRA) less than 40% (unsensitized). Sixteen patients received at least their second allograft or had PRA of 40% or more (sensitized). Average follow-up was 17.9 +/- 8.2 months. Nine patients (15%) failed conversion as manifested by the need to restart cyclosporine 1 to 10 months following conversion. All were in the unsensitized group. Of those successfully converted, there were six allograft failures, two from patient death, one from acute rejection, one from recurrent diabetic nephropathy, and two from patient noncompliance. All were in the unsensitized group, although the difference from the sensitized group was not statistically significant (P = 0.051). There were three rejection episodes, all successfully reversed, in the sensitized group and six rejection episodes in the unsensitized group, five of which were reversed. Overall renal function improved in both groups as shown by a significant decrease in serum creatinine. Neither group required increased doses of steroid to compensate for lack of cyclosporine. From these data we can recommend conversion from cyclosporine to azathioprine in patients with cytotoxic antibodies or those undergoing retransplantation.