Patients undergoing primary cadaveric kidney transplantation were followed for 1 year as part of a phase II, multicenter, open-label concentration-ranging trial of FK506 and cyclosporine. One hundred twenty patients were randomly assigned to a cyclosporine-based regimen or one of three FK506-based regimens designed to achieve low (5-14 ng/ml), medium (15-25 ng/ml), or high (26-40 ng/ml) trough whole blood levels. Corresponding initial doses of FK506 were 0.2, 0.3, or 0.4 mg(kg/day, respectively. Patients with toxicity to FK506 had their target concentration reduced by lowering the dose of FK506. Ninety-two patients completed a 1-year follow-up to determine patient and graft survival and long-term safety. At 1-year, the patient survival rate was 98% for FK506 and 92% for cyclosporine, and the graft survival rate was 93% and 89% in the FK506 and cyclosporine groups, respectively. The incidence of acute rejection was significantly lower (14% FK506, 32% cyclosporine, P=0.048) at day 42 after transplantation. However, the incidence of rejection episodes requiring treatment at 1 year was similar in both groups (33% for FK506 and 32% for cyclosporine). Nephrotoxicity occurred with a similar frequency with FK506 and cyclosporine, but the incidence of neurotoxic events and the incidence of new insulin use were higher among FK506-treated patients. The target range of whole blood levels that optimizes efficacy and minimizes toxicity seems to be 5-15 ng/ml. The corresponding recommended initial dose of FK506 for kidney transplant recipients is 0.2 mg/kg/day. These results indicate that the efficacy and safety of FK506 were comparable to that for cyclosporine for primary immunosuppression in patients undergoing cadaveric kidney transplantation.