We attempted cessation of prednisone therapy in 16 pediatric renal allograft recipients who were between the ages of 3 1/2 and 16 years at the time of transplantation. Fourteen had primary grafts and 2 had second grafts. Nine had cadaver and 7 had living-related donor grafts. At the time of cessation of prednisone, cyclosporine was the only other immunosuppressive therapy for 15 of the patients and 1 patient was receiving CsA and azathioprine. All the patients had stable serum creatinines at the time prednisone was stopped, between 7 months and 5 years posttransplantation. Seven patients have had no episodes of rejection, continuing to receive CsA as their only immunosuppressive therapy and have stable renal function between 16 months and 3 1/2 years (mean: 2 years) after stopping prednisone. Stopping the small maintenance dose of prednisone resulted in improved growth in patients whose epiphyses were not fused. They improved their weight:height ratios and lost their cushingoid appearance. Serum cholesterol levels declined significantly. Patients who required antihypertensive drugs to control their blood pressure while receiving prednisone required fewer or no drugs when off prednisone. Nine patients had acute rejection episodes and were put back on maintenance prednisone following a 3-day steroid pulse. All these patients had a prompt improvement in renal function following the steroid pulse. However, only 3 stabilized function at preprotocol baseline Scr. Four currently have functioning grafts with Scr greater than the preprotocol Scr. Two patients have returned to dialysis. Although stopping steroids is a worthy goal in pediatric renal allograft recipients, we cannot recommend this strategy as routine management because of the 56% rate of acute rejection episodes in the patients who had prednisone withdrawn.