To compare the effect of two immunosuppressive agents, cyclosporin A and tacrolimus, in terms of the development of osteonecrosis after renal transplantation, a cohort study was done. The cyclosporin A group and the tacrolimus group consisted of 32 patients each, and were matched for age, gender, and renal allograft (cadaveric or living). Four patients with osteonecrosis of the femoral head and one patient with osteonecrosis of the knee were observed in the cyclosporin A group, whereas none of the patients in the tacrolimus group had osteonecrosis. All five patients with osteonecrosis were diagnosed on magnetic resonance imaging within 2 years after renal transplantation, and were followed up for more than 3 years after diagnosis. Significant differences were observed in the number of patients with acute rejection (cyclosporin A, 16 patients versus tacrolimus, seven patients). Significant differences also were found in the dose of pulse corticosteroids at 2 weeks (cyclosporin A, 1161.1 +/- 939.6 mg versus tacrolimus, 674.3 +/- 587.5 mg) and 4 weeks after transplantation (1727.5 +/- 1399.9 mg versus 965.0 +/- 861.9 mg). The risk of osteonecrosis after renal transplantation was reduced in the patients who used tacrolimus for immunosuppression, which reduced the number of acute rejection episodes and the dose of pulse corticosteroid administration.