We compared an equine antithymocyte globulin (ATGAM)-based protocol with a Minnesota antilymphocyte globulin (MALG)-based protocol and a murine monoclonal CD-3 (OKT-)-based protocol in 3 groups of heart transplant (HT) recipients. Thirty-four recipients received a four-day course of ATGAM. Thirty HT recipients received a 14-day course of OKT3. Fifteen HT recipients received MALG for an average of 10 days. The ATGAM group received cyclosporine beginning preoperatively, while the OKT3 and MALG groups received CyA beginning on post-transplant day 4. All three groups received identical azathioprine and similar steroid therapy. The 3 groups were similar in age, donor/recipient HLA mismatches, and donor/recipient gender mismatches. The MALG and OKT3 groups had 20% and 17% females, respectively, while the ATG group had 41% (p < 0.05). Average follow-up exceeded 14 months for each group. The ATGAM group received a higher dose of CyA during "induction" therapy than the OKT3 and MALG groups, and experienced a greater rise in post-transplant serum creatinine levels. We found no difference between the 3 groups in: preoperative creatinine levels, one-year post-transplant creatinine levels, number of patients who could be successfully "weaned" from steroids, or one-year survival. Other data are tabulated as episodes/patient: [table: see text] We conclude that ATG plus preoperative CyA is superior for rejection prophylaxis following heart transplantation when compared with either MALG plus postoperative CyA or OKT3 plus postoperative CyA.