15-Deoxyspergualin is a synthetic polyamine that exhibits a novel spectrum of immunosuppressive activity in lower mammals. To define the clinical potential of this drug, we performed 25 abdominal heterotopic heart transplants in Macaca fasicularis. Donor and recipient pairs were selected from ABO-identical animals with negative erythrocyte crossmatches. All recipients received one dose of methylprednisolone sodium succinate at graft reperfusion. Five control recipients received no subsequent immunosuppression. Five recipients received high-dose 15-deoxyspergualin (7.5 mg/kg IM). Five recipients received low-dose 15-deoxyspergualin (2.0 mg/kg IM). Five recipients received cyclosporine (1.0 mg/kg IM). Five recipients received both 15-deoxyspergualin (2.0 mg/kg IM) and cyclosporine (1.0 mg/kg IM). Immunosuppressive agents were administered daily, beginning with the morning of operation, and were continued until the animal was killed or 30 days had elapsed. Graft function was assessed by daily palpation. Median graft survival among control recipients was 9 days (range, 6 to 34 days). At the dose used, cyclosporine alone did not influence either graft survival time (median survival, 13 days; range, 7 to 23 days) or rejection grade. Graft survival and rejection grade among recipients treated with low-dose 15-deoxyspergualin were not different from control recipients or those treated with cyclosporine alone (median survival, 10 days; range, 8 to 39 days). One recipient, killed on postoperative day 8, had an intraadominal abscess. In each of the recipients treated with high-dose 15-deoxyspergualin systemic toxicity developed, and the animal was killed when death appeared imminent, although graft contraction remained vigorous (median survival, 28 days; range 25 to 30 days).(ABSTRACT TRUNCATED AT 250 WORDS)