A 65-year-old woman was admitted to hospital because of orthopnea. She had been followed-up for chronic pericardial effusion detected by echocardiography 10 years previously. Initial echocardiography showed that the left ventricular diastolic diameter (LVDd) was 39 mm and percent fractional shortening (%FS) was 33.3%. Neither fluid samples nor a pericardial biopsy specimen identified the etiology. Cardiac tamponade was not evident, and C-reactive protein and creatine-kinase values were within normal limits. During follow-up, the %FS decreased gradually, but the LVDd remained unchanged. On admission, echocardiography showed that the %FS was 12.5% and LVDd was 40 mm. She developed intractable hyponatremic heart failure with bilateral pleural effusion. Autopsy findings revealed that infiltration of small lymphocytes in the epicardium had penetrated into the subepicardial myocardium. The subepicardial myocardium and the interventricular septal myocardium were diffusely replaced by fibrosis, which could have induced restrictive diastolic heart failure and reduced left ventricular contractility. The fibrosis was not detected in the epicardium itself nor the subendocardial myocardium. This is the first report describing diffuse subepicardial myocardial fibrosis in a patient with chronic pericardial effusion and progressive heart failure.