OKT3 is recommended as rescue therapy for cases of steroid-resistant, clinically persistant acute rejection episodes after heart transplantation. In this study we determined the efficacy of such treatment. One hundred thirty-two patients were included in this study. The postoperative immunosuppressive regimen consisted of triple-drug therapy and perioperative antithymocyte globulin. During a follow-up of 10 to 108 weeks (mean, 51 +/- 20 weeks) 281 treatment-requiring acute rejection episodes (International Society for Heart and Lung Transplantation > or = II) were observed. In 29 cases (10.3%) the grade of the acute rejection episodes was either unchanged after two series of intravenous steroid pulse therapy, was worsened after the first steroid course, or the patient experienced clinical deterioration as a result of the acute rejection episodes. These patients were considered to have steroid-resistant acute rejection episodes and received a 10-day rescue therapy with OKT3, followed by control endomyocardial biopsy. In 17 cases, control endomyocardial biopsy revealed normal myocardium (group I). In 10 cases acute rejection episodes remained unchanged (group II); twice a deterioration was found (group III). However, 12 of the 17 patients from group I experienced a rebound of the acute rejection episodes (International Society for Heart and Lung Transplantation > or = II) 1 to 3 weeks later. Side effects of OKT3 treatment were fever, chills, intestinal complications, hemodynamic response, convulsions, and viral infections.(ABSTRACT TRUNCATED AT 250 WORDS)