The value of immunoprophylaxis with monoclonal anti-CD3 antibodies (OKT3) was evaluated in 44 consecutive, nonrandomized heart transplant patients. The control group (n = 22) was treated with polyclonal rabbit antithymocyte globulin (RATG) for 5 days. The study group (n = 22) was treated with OKT3 for 14 days. All patients had identical perioperative immunosuppressive therapy and similar maintenance therapy, with cyclosporine, azathioprine, and low-dose prednisone (starting prednisone: OKT3 group immediately, RATG group 3 weeks [n = 11] or greater than 3 months [n = 11] after transplantation). The mean histologic rejection grade (Texas classification) in the RATG and the OKT3 groups was 2.5 +/- 1.9 and 0.6 +/- 0.8 (p less than 0.005) after 1 week and 4.3 +/- 1.6 and 2.0 +/- 1.5 (p less than 0.001) after 2 weeks, but there was no difference in the first year. The linearized rejection rate (rejections per 100 patient days) was higher in the RATG group in the first 2 weeks (2.6 vs 0, p less than 0.05 respectively, 7.8 vs 0.7, p less than 0.001) and higher in the OKT3 group in the second month (1.4 vs 2.8, p less than 0.01). In the RATG group the rejection rate fell continuously, to 0.1 at the end of the first year, whereas in the OKT3 group it remained 0.4 (NS). The cumulative first-year incidence was similar for persistent rejections (RATG 0.38 +/- 0.29 vs OKT3 0.48 +/- 1.13, NS) and insignificantly higher for severe rejections in the OKT3 group (RATG 0.21 +/- 0.32 vs OKT3 0.49 +/- 1.10). Rejection-related mortality in the first year was 0% (RATG) and 9% (OKT3).(ABSTRACT TRUNCATED AT 250 WORDS)