Among 125,000 patients who underwent coronary arteriography at the Cleveland Clinic Foundation from 1960 to 1988, 128 (0.1%) were found to have 50-99% stenosis of one or both coronary ostia. All cases were associated with minimal or no obstruction in the distal coronary arteries. Thirty-six percent were males and 64% were females. Fifty percent had ostial narrowing of the left main trunk, 41% had ostial narrowing of the right coronary artery, and 9% had bilateral ostial stenosis. Based on angiographic appearance, the patients were categorized into three groups: 1) atherosclerotic (77%), 2) primary (unknown etiology) (13%), and 3) secondary to aortic valve disease (10%). Compared with the other groups, primary solitary coronary ostial stenosis was commonly found in middle-aged premenopausal or postsurgical menopausal females who had few coronary risk factors and were experiencing severe angina symptoms. At autopsy, most cases were atherosclerotic, however, fibromuscular dysplasia may be found in primary solitary ostial stenosis. This rate entity is difficult to diagnose, and is associated with increased risk during cardiac catheterization and bypass surgery. Solitary ostial stenosis should be included in the differential diagnosis of ischemic heart disease, especially in young or middle-aged female patients.