Fifty-one patients underwent operation for "floppy" aortic or mitral valves during a three-year period between 1969 and 1972. Aortic valve disease occurred predominantly in men, while mitral valve lesions were equally distributed between men and women. In all groups, the mean age at operation was in the fifth decade; only patients with Marfan's syndrome came to operation before the age of 30 years. The clinical course was characterized by rapid deterioration in left ventricular failure after the onset of symptoms; an asymptomatic murmur was often present for many years prior to decompensation. Hemodynamic findings showed a wide range of abnormalities, with cardiac index consistently reduced to 1.5 L/m 2 /min ± 0.3 in aortic disease, and 1.6 L/m 2 /min ± 0.4 in mitral disease. At operation the aortic cusps were thin and prolapsing and, in 5 of 11 patients, an aneurysm of the ascending aorta required resection. Mitral valves were soft, voluminous, with elongated and ruptured chordae. Prolapse of the cusps or billowing of a flail segment produced mitral regurgitation. In 3 patients, mitral valve replacement was complicated by acute dissection of the aorta at the site of the aortic clamp; this was diagnosed at operation and successfully repaired in 2 and discovered at autopsy in 1. Histology of the valves confirmed the presence of diffuse myxomatous tissue in all cusps, cystic medial necrosis in the aorta, and varying degrees of collagen disorganization and necrosis in chordae tendineae. There was frequently deposition of similar myxomatous tissue around chordae and on the ventricular endocardium, possibly as a response to friction. Forty-four patients survived operation and have been followed up for periods up to 36 months. There were 2 late deaths, and 2 valves were replaced at a second operation. There has been no evidence of valve dehiscence. It is concluded that heart disease resulting from connective tissue abnormalities is unique in its clinical course, the high incidence of associated aortic aneurysms and ruptured chordae tendineae, and the postoperative complications of valve dehiscence. Homograft replacement has given encouraging results.