An attempt was made to search the mechanism underlying the beneficial effect of blood transfusion effects using the rat renal transplantation model. The mean survival time of (Sprague-Dawley (SD X Wistar)) F1 renal grafts in untreated SD recipients was 11.3 days. Treatment to SD recipients with 1 ml of Wistar whole blood 7 to 21 days prior to transplantation prolonged the mean survival time of (SD X Wistar) F1 renal grafts and maximum effect of prolongation (greater than 81.3 days) was seen when renal transplantation was performed on the 9th day after the treatment. Treatment with Wistar bone marrow cells, red blood cells and platelets 9 days before transplantation prolonged the mean survival time to greater than 41.0 days, greater than 39.3 days and greater than 46.9 days, respectively, whereas no significant effect was observed in the SD recipients pretreated with Wistar thymocytes or with Wistar plasma. Third party blood transfusion also had moderate effects on the prolongation of renal graft survival, but maximum effects of blood transfusion were obtained by donor specific blood transfusion. Sera taken from SD rats at various times after the treatment with Wistar whole blood were assayed for their ability to suppress the mixed leukocyte reaction (MLR) of SD responder and (SD X Wistar) F1 stimulator cells. Suppressor activity rapidly increased with time up to 7 days after blood transfusion. Potent suppression of the MLR was observed with sera obtained between 7 and 15 days after the treatment. Thereafter, suppressor activity gradually decreased but sera obtained even 21 days after the treatment still suppressed the MLR by more than 50%. The experimental results suggest that MLR suppressor factor(s) generated in the recipients by blood transfusion may play an important role in preventing renal graft rejection. Furthermore, not only class II antigens but also class I antigens in the transfusate may be relevant to the immune response which causes a beneficial effect by pretransplant blood transfusion.