M-mode echocardiography and Doppler were used to assess the effects of phosphodiesterase inhibition on subendocardial function in dilated cardiomyopathy, and in particular, to study interactions with both systolic and diastolic left ventricular function. Twelve adult patients with dilated cardiomyopathy were studied (6 ischemic in origin and 6 idiopathic), 7 of whom were being considered for cardiac transplantation. Cardiac index increased without significant change in heart rate or blood pressure. Longitudinal mitral ring motion, which had been uniformly reduced, increased markedly after intravenous milrinone. Left ventricular cavity size decreased, and shortening fraction, posterior wall thickness, and rates of posterior wall thickening and thinning increased markedly. Left atrial pressure decreased, and isovolumic relaxation time increased. However, the peak velocity and duration of the transmitral E wave increased, with no change in the A wave. Improved longitudinal (subendocardial) function was reflected by improved posterior wall dynamics, and early filling, possibly by augmentation of restoring forces. Thus, severely reduced subendocardial function in dilated cardiomyopathy is potentially reversible, with marked effects on systolic and diastolic function. These previously unrecognized actions of milrinone provide further evidence to justify its short-term use in supporting the severely depressed myocardium.