Eighteen abdominal heterotopic cardiac allografts were performed in outbred rhesus primates. For immunosuppression seven animals received six 100-rad/day total lymphoid irradiation (TLI) doses the week preceding transplant and three 3-mg/kg i.m. rabbit antithymocyte globulin (RATG) doses on postoperative days -1, 0, and +1; five animals were given this RATG dose but no irradiation; three were given TLI alone; and three were given no immunosuppressive therapy. Circulating T lymphocyte counts were monitored in all animals (rosettes). Graft survival in the combined TLI-RATG therapy group (169 +/- 15 days) was significantly greater than in untreated (11 +/- 1 days), RATG alone (22 +/- 12 days), or TLI alone (38 +/- 6 days) treated animals (P less than 0.001, 0.0001, and 0.001, respectively). The animals receiving combined TLI-RATG therapy also achieved significantly greater and more prolonged T lymphopenia than that obtained in the other three groups. Six of seven cardiac allografts placed in animals receiving TLI-RATG therapy were removed electively before cessation of electrical activity; however, in four of these rejection pathology was noted. Thus, it seems that combined TLI-RATG therapy may be of benefit in the management of transplant recipients, but its use will probably not abolish these patients' requirements for immunosuppressive maintenance measures.