To determine whether the heart-specific immunoreactivity associated with active myocarditis affects outcome after heart transplantation, we retrospectively analyzed the outcome of 12 patients with active lymphocytic myocarditis in their explanted native hearts identified by the Registry of the International Society for Heart Transplantation. The patients were 38 +/- 10 years of age and predominantly female (75%). In nine patients (75%), endomyocardial biopsy showed active myocarditis before transplant; eight of these patients also received immunosuppression before transplant. Recipient hemodynamic study before transplantation demonstrated an ejection fraction of 0.18 +/- 0.06, cardiac index of 1.7 +/- 0.4 L/min/m2, pulmonary artery pressure of 41 +/- 6/23 +/- 6 mm Hg, and mean pulmonary capillary wedge pressure of 30 +/- 5 mm Hg. Left ventricular end-diastolic dimension by echocardiography was 6.0 +/- 1.4 cm. Four of the patients were dependent on intravenous inotropes, and six required mechanical assistance. Over a 36-month follow-up period, 2.9 +/- 2.4 episodes of rejection occurred per patient. Sixty percent of the first episodes occurred within 2 weeks of transplantation. These patients experienced a 2.2 +/- 1.1-fold increase in rejection compared with institutional average rejection rates. Survival was significantly shorter than that of age-matched or female control subjects. This study is limited by its retrospective nature and the unusual pretransplant characteristics of the subjects. It indicates that active myocarditis may predispose patients to early severe rejection and a high mortality rate after heart transplantation.