The role of ABO blood group compatibility on graft survival when transplantation is performed between closely related animal species is uncertain. Heart transplants (in the neck) were performed between donor vervet monkeys and recipient baboons; no immunosuppressive therapy was given. Survival in ABO-compatible pairs (group 1, n = 9) was for a mean of 10.3 (± 5.2) days, which was not significantly different from that in ABO-incompatible pairs (group 2, n = 9: mean survival 7.3 ± 5.6 days). In group 2, however, three hearts were rejected hyperacutely within 60 minutes, whereas in group 1 only one heart was rejected within 24 hours (not significant). Performed anti-vervet monkey antibody was present in only one of 18 baboons, but developed in eight others. ABO-specific antibodies were present in all nine group 2 baboons and increased in titer in six cases. Histopathologic features of vascular (humoral) rejection, sometimes associated with cellular infiltration, were seen in a majority of hearts in both groups. Though the number of animals in this study was small, ABO-incompatibility would not appear to be a major factor in cardiac xenograft survival when transplantation is performed between closely related primate species, though early hyperacute rejection would seem more likely to occur when blood group incompatibility is present.