Two hundred nineteen consecutive patients referred for echocardiography were analyzed to determine the occurrence of mitral regurgitation (MR) in the absence of intrinsic abnormalities of the mitral leaflets. MR was assessed by means of the pulsed-Doppler technique. There was a higher incidence of MR associated with absence of mitral leaflet abnormalities compared to the presence of these abnormalities (59% vs 41%, p less than 0.01). The most common causes of MR were mitral annular calcification (MAC) and incomplete mitral leaflet closure (IMLC). The extent of calcific deposit in patients with MAC and the distance from the mitral leaflet coaptation point to the mitral annular plane in systole patients with IMLC correlated well with the severity of MR by Doppler technique (rho = 0.91 and 0.71, respectively). To determine the mechanisms of MR in these two conditions, 29 consecutive patients with MAC and 28 with IMLC were referred to the echocardiography laboratory, and 10 age-matched control subjects were prospectively analyzed. Patients with MAC had a 50% reduction in the sphincteric action of the mitral anulus in systole compared to control subjects. All patients with IMLC had poor left ventricular systolic function; most had left ventricular, mitral annular, and left atrial dilation, and only eight had regional wall motion abnormalities. When discriminant function analysis was used, poor left ventricular systolic function was the principal variable that separated patients with IMLC from normal subjects (F = 81.6, p less than 0.0001). We conclude that: (1) MR in adults occurs most commonly in the absence of intrinsic abnormalities of the mitral leaflets, primarily those resulting from MAC and IMLC; (2) MR in patients with MAC results from a reduced sphincteric action of the mitral anulus in systole; and (3) IMLC results from poor left ventricular systolic function, irrespective of the cause.