Recent evidence suggests that regression of left ventricular hypertrophy (LVH) with antihypertensive therapy improves prognosis. The mechanism for this benefit is unknown but may be related to effects on myocardial performance. Midwall fractional shortening (mFS) is often depressed in patients with asymptomatic hypertension, is associated with LVH, and is a potent, independent predictor of outcome. We therefore examined whether antihypertensive therapy may improve midwall performance. mFS as well as conventional echocardiographic parameters were measured serially among 29 hypertensive persons during 6 months of drug therapy. Stress-adjusted and absolute midwall function improved by 10% and 11%, respectively (p <0.05), whereas no significant changes were detected in other measures of chamber function. Improvement in function was more pronounced in patients with concentrically remodeled ventricular geometry and in those who achieved greater reductions in left ventricular (LV) mass. Antihypertensive therapy and LV mass regression is associated with demonstrable improvements in cardiac performance when assessed using mFS. Determinations of mFS may have a promising role in identifying patients with early hypertensive heart disease, tracking responses to therapy, and in elucidating the potential beneficial effects associated with LV mass regression.