Prolactin, a pituitary hormone, has been shown to have an active role in the regulation of the immune system. Prolactin receptors have been described on the membrane of lymphocyte cells, and competitive binding to these receptors by cyclosporine and circulating prolactin has been demonstrated. Experimental evidence suggests a synergistic effect of cyclosporine and bromocriptine, an inhibitor of pituitary release of prolactin, on immunosuppression. Between July 1986 and January 1988, 54 patients were randomly assigned to two groups of immunosuppression treatment. Thirty patients (group 1) were administered cyclosporine, azathioprine, and prednisone and 24 patients (group 2), a modified protocol aimed at decreasing the level of circulating prolactin by adding bromocriptine to the immunosuppression regimen. The two groups were similar in regard to age, preoperative diagnosis, and duration of follow-up. Minimal side effects related to bromocriptine were observed. The overall incidences of rejection and infection were similar, although actuarial analysis showed that freedom from these complications among patients treated with bromocriptine was significantly higher throughout the first 2 months after heart transplantation compared with that of patients in the control group. Other variables such as serum cyclosporine levels and lymphocyte counts were similar in both groups. In conclusion, suppression of circulating prolactin by bromocriptine appears to improve the immunosuppressive effect of cyclosporine, at least during the early postoperative period when the risk of rejection and infection is higher, and could be a promising avenue to successful hormonal manipulations of the immune process after organ transplantation.