The hemodynamic changes following elevation of systemic arterial pressure and total systemic resistance by methoxamine were studied by right heart catheterization in 18 patients with mitral valve disease and 4 patients with no significant cardiovascular abnormality. This is the first detailed report of the circulatory effects of this drug in man. Changes in oxygen consumption, arterial oxygen saturation, stroke index and pulmonary artery to pulmonary “capillary” mean pressure gradient were insignificant. Forward cardiac index and heart rate decreased significantly while arteriovenous oxygen difference increased markedly in all groups of patients. The hemodynamic mechanisms involved in the changes observed during methoxamine infusion are discussed. Characteristic of patients with mitral insufficiency were significant increments of pulmonary arterial mean, pulmonary “capillary” mean, and pulmonary “capillary” V peak pressures. These subjects also had significantly greater increments in “left heart” resistance than patients without mitral insufficiency. An elevation of pulmonary “capillary” V peak pressure of 35 per cent or more of the elevation of systemic arterial systolic pressure was found to be a useful index of the presence of mitral insufficiency. Study of the pulmonary “capillary” pressure records during methoxamine infusion may obviate the necessity of left heart catheterization in the detection of significant mitral insufficiency.