The aim of our study was to investigate the pathogenesis of the global biventricular dysfunction observed in patients with critical coronary artery stenosis, but no evidence of myocardial ischemia or infarction. From January 1992 to January 1997, among consecutive patients undergoing invasive cardiac study including biventricular endomyocardial biopsy because of progressive heart failure (NYHA functional class III-IV) associated with biventricular dysfunction and no history of myocardial ischemic events, 7 patients had severe coronary artery disease (three vessel 4 patients; two vessel 1 patient, proximal occlusion of left anterior descending artery 2 patients). At two-dimensional echocardiography left and right ventricular end-diastolic diameter were 73 +/- 10.5 and 39 +/- 7 mm, respectively, left ventricular ejection fraction was 0.23 +/- 6.5 and right ventricular ejection fraction was 0.29 +/- 7.2. Histology showed extensive lymphocytic infiltrates with focal myocytolysis meeting the Dallas criteria for myocarditis in all patients. Two patients with active inflammation received prednisone and azathioprine in addition to conventional drug therapy for heart failure. At 6-month follow-up cardiac volume and function improved in immunosuppressed patients (left ventricular ejection fraction from 15 to 50% and from 20 to 38%, respectively) while they remained unchanged in conventionally treated patients. In conclusion, global biventricular dysfunction in patients with severe asymptomatic coronary artery disease and no evidence of previous myocardial infarction may be caused by myocarditis rather than by myocardial ischemia or hibernation.