Acute viral myocarditis triggers an autoimmune phenomenon that aggressive immunosuppressive therapy with monoclonal OKT3 may suppress. We treated 5 patients, aged 15 months to 16.5 years, who had acute viral myocarditis and left ventricular ejection fraction (LVEF) of 5% to 20%, with a combination immunosuppressive regimen that included OKT3, intravenous immunoglobulin, methylprednisone, cyclosporine, and azathioprine. Within 2 weeks of therapy, all patients demonstrated normalization of LVEF to 50% to 74%, and on mid-term follow-up, we have found no recurrence of heart failure or progression to dilated cardiomyopathy. In patients with severe acute myocarditis, aggressive immunosuppressive regimen based on OKT3 is safe and may inhibit or reverse the immune response, resulting in dramatic improvement in myocardial function.