The treatment of pediatric acute myocarditis that is hemodynamically significant often includes immune modulation with intravenous immunoglobulin (IVIG) and steroids, and supportive measures. In this population, published outcomes include recovery of ventricular function from 6 months to years, transplantation, or death. We studied the effect of the immunosuppressive agent muronomab-CD3 (OKT3) on recovery of heart failure in the treatment of pediatric myocarditis. A retrospective chart review was performed identifying 15 pediatric patients diagnosed with acute myocarditis and depressed left ventricular ejection fraction (LVEF) or arrhythmias to which OKT3 was added to the immunosuppressive regimen. All patients were treated with supportive care, intravenous immunoglobulin, and steroids. LVEF by echocardiogram was plotted for each patient versus time. Outcomes included recovery of left ventricular function (as defined by an LVEF > or = 45%), death, or listing for transplant. The diagnosis of acute myocarditis was made by a positive endomyocardial biopsy in 8 patients. Nine patients required extracorporeal membrane oxygenation (ECMO) or LV assist device. After treatment with OKT3, 9 patients made a significant recovery of LVEF within 17 days, and 1 recovered by 60 days. Six of the patients requiring mechanical assistance recovered within this time period. There were 4 deaths--3 due to ECMO complications and 1 due to underlying gastrointestinal illness. One patient diagnosed with chronic myocarditis on biopsy underwent transplantation. No significant side effects attributable to OKT3 occurred. By decreasing the autoimmune inflammatory response, OKT3 may hasten recovery of ventricular function and be a useful adjunct therapy for hemodynamically significant acute pediatric myocarditis.