Although cyclosporine has improved allograft survival in renal transplant patients, problems with drug toxicity remain, raising the question whether cyclosporine should be stopped at some point post-transplant. However, the relative safety of converting from cyclosporine to another immunosuppressive agent, or simply stopping cyclosporine remains an issue of debate and has not been evaluated in children. We have developed a protocol to convert children, who are 6 months post-transplant and have stable kidney function, from cyclosporine and prednisone to azathioprine and prednisone. Eleven children have undergone conversion because of suspected/potential nephrotoxicity or because of other difficulties with cyclosporine (expense, hirsutism). These children were compared with a control group of 12 children who met all criteria for conversion at 6 months but remained on cyclosporine. Allograft survival was similar in both groups but the children converted from cyclosporine experienced an improvement in renal function as measured by calculated creatinine clearance. There were no episodes of rejection for a period of 4 months post-conversion and all rejection episodes that developed subsequently occurred during or after the change from daily to alternate-day prednisone. We believe that conversion from cyclosporine to azathioprine can be accomplished safely in children with stable allograft function but long-term risks and benefits need further evaluation.