In a series of more than 8000 first cadaver transplants performed during a two-year period, 2198 recipients treated with cyclosporine had a higher graft survival rate (76 +/- 1% at 1 year) than 6392 recipients without cyclosporine (64 +/- 1%, P less than 0.0001). Matching for HLA-B plus HLA-DR resulted in a significant correlation with graft outcome, in patients with or without cyclosporine treatment (P less than 0.0001). Regardless of whether cyclosporine was used or not, grafts with 0 HLA-B,-DR incompatibilities had approximately 20% higher success rates at one year than grafts with 4 mismatches. A high (86 +/- 3%) graft survival rate was obtained in 161 cyclosporine-treated recipients with 0 HLA-B,-DR mismatches. Matching for the HLA-B and HLA-DR loci is shown to have an additive effect in cadaver kidney transplantation.