A prospective study was performed in moderately immunosuppressed unrelated rhesus monkeys to investigate the influence of a single transfusion on kidney allograft survival. The recipients received either whole citrated blood or plasma-free transfusates consisting of pure red blood cell or lymphocyte suspensions. Except for one group, in which blood and kidney donors were optimally matched, transfusions and kidney allografts were disparate for two to four A/B locus antigens with the recipients. Transfusions were given 2 to 4 weeks before kidney grafting, except in one experimental group where the recipients were transfused 0 to 12 hr before transplantation. The general trend was that graft prolongation could be obtained with all experimental protocols. However, it was also shown that a single transfusion entails the risk of accelerated rejection. This adverse effect was not observed in the animals receiving blood and kidneys from donors optimally matched for A/B locus antigens and in recipients transfused shortly before or during transplantation. These results may contribute to a further improvement of the current clinical transfusion policy.