The baboon, like the human, expresses A and/or B blood group antigens on its tissues. Anti-A and anti-B antibodies are directed against these antigens, the epitopes of which are carbohydrate structures. Portions of these carbohydrates have been synthesized (trisaccharides A and B, respectively). When infused intravenously, the synthetic trisaccharides form a complex with the specific antibodies and neutralize their activity preventing them from binding to the antigen targets on a transplanted organ. In nonimmunosuppressed, hyperimmunized baboons, the continuous intravenous infusion of the specific trisaccharide alone (for 6 days) inhibited rejection of ABO-incompatible cardiac allografts, extending survival from a mean of 19 min (n = 3) to 8 days (n = 2), at which time the grafts failed from cellular (not vascular) rejection. The combination of long-term pharmacologic immunosuppression plus trisaccharide infusion (for periods of 8 to 19 days) extended survival to a mean of > 28 days (n = 4) with one heart functioning > 52 days. Accommodation clearly occurred in three of the four cases. This form of therapy may permit cadaveric organ allotransplantation across the ABO blood-group barrier in the human.