Severe mitral regurgitation (MR) due to coronary artery disease unfavorably alters prognosis for medical therapy and is also associated with increased surgical mortality. In this report, the clinical, angiographic and pathoanatomic findings in 50 consecutive patients with severe ischemic MR were characterized. Forty-two patients (84%) either presented with acute myocardial infarction or a well-documented prior infarction. Eleven patients (22%) were in cardiogenic shock at the time of catheterization. Forty patients (80%) had greater than 70% stenosis of the right and left circumflex coronary arteries with or without left anterior descending coronary artery stenosis. Segmental asynergy of the left ventricular wall was present in 48 patients (96%) and involved the inferior wall in 43 (86%). Mean ejection fraction for the group was 51 +/- 7%. A total of 15 patients had direct inspection of the mitral valve apparatus at surgery or autopsy. Posteromedial papillary muscle involvement was found in 14 patients, fibrosis or necrosis in 10 and rupture in 4, with anterolateral papillary muscle rupture in 1 patient. Thus, acute severe ischemic MR is usually associated with significant narrowing of both right and left circumflex coronary arteries, and posteromedial papillary muscle involvement.