Reversal of left ventricular (LV) hypertrophy with medical therapy has been studied increasingly in patients with systemic hypertension. However, serial changes of LV function are not found during reversal of LV hypertrophy in hypertensive patients. Seven patients with LV hypertension were studied to evaluate serial changes of LV mass and function after the initiation of the new converting enzyme inhibitor MK-421. LV mass and function were determined serially at the end of a placebo period and at 5 days, 1 month, 3 months and 7 months after the initiation of MK-421, using both 2-dimensional (2-D) guided M-mode echocardiography and radionuclide techniques. All patients except 1 had LV hypertrophy and all had normal LV function (ejection fraction derived from gated blood pool method greater than 49%). There was an inverse relation between LV fractional shortening (percent FS) and end-systolic stress before medication (r = -0.81, p less than 0.05). LV mass decreased significantly at 3 months and at 7 months (-10%, p less than 0.05, and -12%, p less than 0.01, respectively) accompanied with persistent decrease of mean blood pressure, which occurred as early as 5 days after start of therapy (133 +/- 5 mm Hg at control, to 112 +/- 4 mm Hg at day 5). During reversal of LV hypertrophy, the inverse correlation between FS and end-systolic stress remained significant (r = -0.80 to -0.95, p less than 0.025 for all), with no difference from the placebo period and from this relation in the normal group. Moreover, percent FS, ejection fraction and stroke index remained unchanged. Thus, LV hypertrophy in patients with systemic hypertension can be reversed without deterioration of LV function. Moreover, overall LV function is likely to be determined by afterload even after reversal of LV hypertrophy.