The complications of long-term steroid immunosuppression are well known. During a 12-month period, 52 living-donor renal transplant recipients were entered into a protocol of intentional early steroid withdrawal. Selection criteria were primary living-related renal transplants in HLA-identical (12) or one-haplotype match (40) patients. The study population consisted of 25 diabetics (48.1%) with a mean age of 32.4 years. All patients received preoperative blood transfusions (3 donor-specific in haplotype-matched, 3 random in HLA-identical recipients). Immunosuppression consisted of cyclosporine, azathioprine, and corticosteroids, with deliberate steroid withdrawal after two weeks. Forty-six patients (88.5%) were successfully tapered off steroids, while the six protocol failures (11.5%) were due to early rejection or leukopenia that prevented steroid withdrawal. Twenty-three patients (50%) subsequently were returned to steroid therapy for rejection (21) or leukopenia (2). Inadequate immunosuppression precipitated six rejection episodes and were preventable, while the remaining 15 were true breakthrough crises. The overall rejection rate was 50%, with 92.3% of initial rejection episodes occurring within five weeks of steroid withdrawal. Rejection episodes were responsive to steroid therapy alone in 73.2% of cases. No graft loss from rejection has occurred after a mean follow-up interval of 8.5 months. At present, 33 patients (63.5%) are off steroids. In HLA-identical recipients, all but one successfully completed the protocol and 75% are currently steroid-free. In haplotype-matched patients, 87.5% completed the protocol and 60% are steroid-independent. Comparison with well-matched control groups on steroids failed to reveal any difference in graft or patient survival, rejection, infection, or mean serum creatinine level. No discriminating risk factors could be identified that were predictive of steroid withdrawal success or failure. In select patients, early steroid withdrawal can be accomplished without jeopardizing graft function. Long-term follow-up is required to assess the risk-benefit ratio of steroid withdrawal upon immunosuppressive morbidity.