To assess the relative contributions of afterload mismatch and impaired contractility to pump dysfunction in patients with chronic aortic valve disease, simultaneous left ventricular cineangiography and micromanometry were performed in 56 patients: 21 with severe aortic stenosis, 16 with severe aortic regurtitation, and 19 normal control subjects. Left ventricular mass was increased in patients with aortic stenosis and aortic regurgitation (172 + 52 and 224 ± 63 g/m2, respectively, vs 89 + 16 for control subjects; p < .05) as were end-diastolic volume (101 ± 39 and 167 ± 44 vs 77 + 16 ml/m2; p < .05) and end-systolic volume (50 + 40 and 84 ± 43 vs 24 7 ml/m2; p < .05). Although ejection fraction was depressed in both abnormal groups (0.56 ± 0.18 for patients with aortic stenosis and 0.53 + 0.13 for those with aortic regurgitation vs 0.69 0.05 for control subjects; p < .05), the decrease in ejection fraction was disproportionate to the mild degree of afterload mismatch (end ejection stress 129 + 17 in patients with aortic stenosis and 154 ± 58 in those with aortic regurgitation vs 117 46 kdyn/cm2 in control subjects; p = NS) with 10 of 21 patients with aortic stenosis and 12 of 16 patients with aortic regurgitation falling below the 95% prediction limit of the linear inverse relationship between ejection fraction and end-systolic stress for controls (EF = 0.78 – 0.00074.ESS). The maximum stress:volume index ratio, which is an index of inotropic state that is independent of preload but sensitive to afterload, was also depressed in patients with aortic stenosis and aortic regurgitation (3.8 ± 1.4 and 2.5 ± 0.9 vs 5.0 1.3 kdyn/cm5/m2 for control subjects; p < .05), and first-order partial correlation demonstrated that this decrease was inversely related to left ventricular mass index. Thus, although afterload mismatch may adversely affect ventricular performance in patients with aortic valve disease, extensive hypertrophy and contractile dysfunction appear to be the major determinants of pump dysfunction.