To evaluate the risk/benefit ratio of perioperative OKT3 in cardiac transplant patients receiving triple-drug immunosuppression, patients who underwent cardiac transplantation between July 1, 1988 and December 31, 1989 (n = 33) and who received perioperative OKT3 were retrospectively compared with patients who underwent transplantation between January 1, 1990 and June 30, 1991 (n = 46), and who received no perioperative anti-T cell therapy. To allow similar follow-up, data were analyzed through June 30, 1990 for the OKT3 group and through December 31, 1991 for the no anti-T cell therapy group. Patients in the no anti-T cell therapy group waited longer for a donor organ; other pretransplant characteristics did not differ. The azathioprine dose 1 month after transplant was higher in the no anti-T cell therapy group (144 +/- 63 mg vs 109 +/- 55 mg, p = 0.016); other post-transplant immunosuppression was similar. The incidence of total and treated rejection and the time to the first rejection did not differ between the groups. The OKT3 group had a higher number of infections (0.8 +/- 0.9 vs 0.3 +/- 0.3, p = 0.006) and intravenously treated infections (0.5 +/- 0.6 vs 0.1 +/- 0.2, p = 0.004) per patient per month. Cytomegalovirus infection developed in 46% of the OKT3 group versus 22% of the no anti-T cell therapy group (p = 0.025). Patient survival did not differ between the groups. Thus, an immunosuppressive regimen that includes perioperative OKT3 increases infections, especially cytomegalovirus infections, without decreasing or delaying rejection or increasing survival.