Alterations in left ventricular (LV) mechanics have significant effects on myocardial oxygen consumption (MVO2) as a result of changing LV pressure and dimensions. However, the effects of load alteration on MVO2 in the setting of LV hypertrophy and LV dysfunction have not been well characterized. Therefore, we examined changes in LV mechanics and MVO2 in 32 patients with varying degrees of LV hypertrophy and LV dysfunction before and after pharmacologic alteration of load. With phenylephrine or nitroglycerin-induced load alteration, changes in peak systolic meridional stress, mean systolic stress and the area of a stress-dimension loop all correlated modestly with changes in MVO2 (r = 0.66, 0.62, 0.63, respectively). However, changes in the time integral of LV ejection stress, or shortening load, were significantly correlated with changes in MVO2 (r = 0.88, p less than 0.001). In particular, load reduction results in a beneficial effect on MVO2. In addition, for a given change in LV systolic pressure, changes in shortening load (38 +/- 3.7%) were significantly greater than changes in tension-time index (13 +/- 1.4%), thus providing a sensitive marker of alteration of mechanical load. We conclude that physiologic alterations in mechanical load in normal persons as well as patients with LV hypertrophy are reflected in significant changes in the time integral of LV ejection stress. These changes in shortening load, mediated by changing LV pressure and dimension, are significantly related to changes in MVO2.