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The benefits and risks of cyclosporin withdrawal after renal transplantation is controversial. The purpose of this study is to compare the long-term graft survival effects of two protocols of cyclosporin withdrawal. From March 1986 to July 1992, 64 adults, nondiabetic renal transplant recipient with stable renal function on prophylactic triple therapy participated in these protocols. In the Group I (n=34) the elective cyclosporin was withdrawn from 6th to 12th month after transplantation and in the Group II (n=30) during the second year. The average preconversion posttransplant follow-up was 5,1+_2,4 months in Group I (G I) and 17,9+_5,1 months in Group II (G Il). There was no difference in sex, source of donor, acute rejection (AR) episodes frequency and mean serum creatinine between groups before conversion. The mean follow-up postconversion was also similar (G I: 67,4+_38,2 x G II: 61,5+25,3 months). In G I five (14,7%) patients presented acute rejection episodes while six patients (20%) presented it in the G II (p=ns). Four from these 6 patients had a renal biopsy irnrnediately preconversion, in 3 the specimens showed focal mononuclear infiltration and one was normal. All of them were treated with methylprednisolone pulse and cyclosporin was restarted. The response to rejection treatment was partial in 4 (80%) of the G I and in 3 (50%) patients of the G II. There was one (16,7%) graft loss in G II due to acute rejection. From patients who did not present AR episode cyclosporin was restarted in 6 (20%) patients in the G I and in only one (4,2%) in the G II. From the whole sample 25,4% developed chronic rejection (CR), being 14 (41,2%) in G I and 4 (13,8%) in G II (p=0,014). In the G I, from the 29 patients who did not present acute rejection episode postconversion, only 8 (27,6%) had grail loss due to (CR) while 4 (80%) from 5 patient who presented AR (p=ns). In G II it happened in 1 (20%) from the 5 patients who present AR and 3 (12,5%) from 24 without AR. The actuarial graft survival at third and fifth year after transplantation was, respectively, 75,8% and 51,5% in the G I and 89,7% and 78,9% in the G II (p=0,02), however excluding death as a cause of graft loss the actuarial graft survival is similar is both groups. The cyclosporin withdrawal was associated with a high frequency of acute rejection episodes. The incidence of chronic rejection was higher in Group I, however it was not directly the cause of lower actuarial graft survival in this group.