A total of 20 renal transplant patients with end-stage diabetic nephropathy entered a randomized controlled trial comparing preoperative, fractionated total lymphoid irradiation (TLI) (radiation dose, 20-30 Gy) with postoperative cyclosporin A (CsA). Both groups received postoperative low-dose methylprednisolone maintenance therapy. The 3-year patient and graft survival was similar for both groups (100% and 71% in the TLI and 75% and 75% in the CsA group, respectively). Rejection crises occurred significantly more frequently (P less than 0.01) in the TLI-treated recipients. The incidence of infectious or diabetic complications was not significantly different in both groups. It is concluded that TLI and CsA are both effective treatment modalities for cadaveric renal transplantation in diabetics; CsA, however, is superior in preventing rejection crises.