Baboon hearts were rapidly excised after being flushed with 500 ml of cardioplegic solution at 4°C and then immersed in cold 4° C saline or cardioplegic solution for 2 minutes. The hearts were then perfused at 8 to 10 cm H2O pressure for 20 to 24 hours under refrigeration with a hyperosmolar clear fluid perfusate at 6 to 8°C, through which 95% oxygen and 5% carbon dioxide were continually bubbled to maintain the perfusate pH between 7.2 and 7.4. Myocardial temperature remained at approximately 6 to 8°C. The hearts were then orthotopically transplanted into recipient baboons matched for size and AB blood group. Two groups (A and B) were studied, differing significantly only with respect to the constitution of the cardioplegic solution and perfusate used. The cardioplegic agent used in Group B contained a higher concentration of magnesium than that used in Group A and included the calcium antagonist verapamil. Perfusate B had higher osmolality than perfusate A, largely due to the inclusion of sucrose. A preliminary group of 10 baboons in Group A received no immunosuppression. Five of the remaining six immunosuppressed baboons in this group survived more than 48 hours to rejection or until killed at 2 to 29 days. All six of the baboons in Group B survived to rejection between 6 and 33 days, with mean survival 19.5 days. Cardiac catheterization was performed in six surviving baboons (Group A, four; Group B, two) between postoperative days 6 and 10 and showed good hemodynamic function. Histologic examination of hearts after death has shown only minor ischemic changes in those hearts which functioned well.