In the rat a single i.v. injection of donor whole blood (0.5 ml) 7 days before a renal allograft leads to complete suppression of rejection and permanent acceptance of the graft in DA(RT1a)-to-LEW(RT1(1], LEW-to-DA, and (DA X LEW)F1-to-DA combinations. This effect is donor-specific. Purified erythrocyte preparations were used for pretreatment (8 X 10(9) erythrocytes) 7 days before transplantation in the same strain combinations. The contamination by leukocytes was 1300 per 8 X 10(9) erythrocytes after one method of preparation, but only 1.3 per 8 X 10(9) erythrocytes after further purification by affinity chromatography. Both preparations of purified erythrocytes were able to suppress rejection and induce permanent acceptance of an allograft. The role of contaminating leukocytes in the first preparation was further excluded by pretreating rats with 1300 lymphocytes, but in these animals allografts were rejected in the normal fashion. The effect of the erythrocyte pretreatment was donor-specific, dose-dependent, only effective if given by the i.v. route, and not effective if given less than 7 days before transplantation. Furthermore neither lymphocytotoxic nor erythrocyte binding antibody could be detected in rats pretreated with purified erythrocytes. These experiments show convincingly that, in the rat--in the strain combinations tested--pretreatment with erythrocytes, that express cell surface class I MHC antigens, but not class II products, can induce specific suppression of rejection of a renal allograft.