OKT3 is a murine monoclonal antibody that is reactive against the CD3 surface antigen on T lymphocytes. This antigen appears to be essential for recognition of foreign antigen and for initiation of the process of cell-mediated rejection. One hundred and two patients having orthotopic cardiac transplantation in a single program during a 3-year period received prophylactic immune suppression with OKT3, along with azathioprine and low-dose steroids. Patients began receiving cyclosporine on Day 11; steroid-weaning was attempted 3 weeks after transplantation. In this group of patients, the time to the first rejection was 76 +/- 11 days (mean +/- SEM), and 85% were successfully weaned from maintenance steroids. Avoidance of the side effects of cyclosporine and/or high dose steroids during the perioperative period, combined with a long rejection-free interval and the likelihood of long-term maintenance free of steroids, make the use of OKT3 or similar agents an attractive alternative to conventional immunosuppression.