Pressure overload hypertrophy of the left ventricle due to aortic stenosis is associated with abnormalities of left ventricular isovolumic relaxation and early diastolic filling. The relative contribution of the hemodynamic load on the left ventricle to the impairment of diastolic function observed in this disorder remains poorly understood. To study this relation, the vasodilator nitroprusside was administered to eight patients with aortic stenosis and normal systolic function. The effect of a short-term reduction in left ventricular preload and afterload on left ventricular isovolumic relaxation and early diastolic filling was assessed by analysis of simultaneous micro manometer left ventricular pressure and radionuclide angiographic volume measurements. At baseline, left ventricular systolic and end-diastolic pressures were markedly elevated, and associated with prolongation of the time constant of left ventricular relaxation and depression of the left ventricular peak filling rate. Infusion of nitroprusside resulted in reduction of left ventricular systolic (204 ± 31 to 176 ± 31 mm Hg, p > 0.05) and end-diastolic (31 ± 8 to 18 ± 6 mm Hg, p > 0.05) pressures, with no associated improvement in time constant of left ventricular pressure decay (T) (68 ± 25 to 80 ± 37 ms, p = NS), T 1/2 (34 ± 8 to 34 ± 14 ms, p = NS), left ventricular peak filling rate (2.3 ± 0.5 to 2.3 ± 0.8 end-diastolic volume/s, p = NS) or time to left ventricular peak filling rate (150 ± 50 to 144 ± 37 ms, p = NS). These data suggest that in patients with pressure overload hypertrophy and preserved systolic function, impaired left ventricular relaxation and early diastolic filling are not improved by short-term reduction of ventricular loading conditions. The impairment of diastolic function observed in such patients may reflect an intrinsic abnormality of hypertrophied myocardium or the influence of ischemia.