Eight freshly excised pig hearts were hemoperfused by baboons in vivo. Cardiac function ceased in six hearts after a mean period of 90 minutes of perfusion (range 30 to 190 minutes). Two hearts continued functioning for the 4-hour study period. On microscopic examination, seven hearts, including one that continued beating, showed histopathologic features of hyperacute rejection. IgG, IgM, and C3 were strongly present on the myocardium in all cases. Hemoperfusion was associated with significant increases in heart mass (p less than 0.002) and circulating polymorphonuclear leukocytes (p less than 0.03) and reductions in coronary blood flow (p less than 0.0001), circulating lymphocytes (p less than 0.03), and C4 (p less than 0.03). Preformed circulating anti-pig antibodies disappeared in all but one baboon. Hyperacute rejection in this discordant xenograft model that used a nonhuman primate as "recipient" differs in few aspects from that seen in other experimental models. Possible methods of prolonging xenograft survival are discussed.