The routine use of monoclonal induction immunosuppression with OKT3 after orthotopic heart transplantation remains controversial. This study examined the clinical response of prophylactic monoclonal induction immunosuppression versus standard triple-drug immunosuppression in 41 patients who underwent orthotopic heart transplantation from January 1989 to December 1990 at this institution. Of these, eight received monoclonal induction immunosuppression for a period of 10 to 14 days. All patients received identical triple-drug immunosuppression with the exception of cyclosporine starting on the fifth postoperative day in those who received OKT3. At 6 months the duration of hospitalization, freedom from rejection, incidence of infection requiring hospitalization, and serum creatinine in the monoclonal induction immunosuppression and triple-drug groups were compared. It was found that the length of hospital stay in the OKT3 group was 14.3 +/- 4.5 days, compared with 14.7 +/- 4.7 days in the triple-drug group and that freedom from rejection was 66% in the OKT3 group compared with 75% in the triple-drug group. In addition, it was found that the incidence of infection was 36% in the OKT3 group compared with 38% in the triple-drug group and that serum creatinine at 6 months was 1.36 +/- 0.26 mg/dl in the OKT3 group compared with 1.45 +/- 0.73 mg/dl in the triple-drug group. Finally, patient survival at 1 year for the monoclonal induction immunosuppression group was 100% compared with 91% for the triple-drug group.(ABSTRACT TRUNCATED AT 250 WORDS)