Muromonab-CD3 (Orthoclone OKT3) monoclonal antibody was used as immunosuppressive therapy in 24 selected, cyclosporine-treated heart transplant recipients. Patients included 15 men, eight women, and one child. Mean age was 47 years. Eight patients (group 1) received OKT3 as rescue therapy for rejection, eight (group 2) as primary therapy for rejection, and eight (group 3) as induction therapy. Drug efficacy in the reversal or prevention of rejection in group 1 was 71%; in groups 2 and 3 it was 100%. Recurrent rejection occurred in three of 20 (15%) patients, despite optimal cyclosporine maintenance therapy after OKT3 therapy. Two patients were re-treated successfully for rejection with second courses of OKT3. Systemic side effects occurred in all patients, but in no case did they necessitate cessation of therapy. Infectious complications occurred in all except one patient, typically within the first month after therapy. On the basis of this experience, OKT3 therapy appears highly effective in reversing and preventing cardiac allograft rejection. Further research of the potential complications of such therapy is required to establish optimal dosing schedules and indications for its use after heart transplantation.