C-11 acetate has recently been introduced as a tracer of myocardial oxidative metabolism with the use of positron emission tomography. To evaluate this approach in the pressure- or volume-loaded heart, C-11 acetate clearance rate constants were determined in 22 patients with chronic aortic valve disease and in nine normal subjects. Global myocardial C-11 clearance was significantly higher in patients with predominant aortic stenosis (n = 11) or aortic regurgitation (n = 11) than in normal subjects (0.069 +/- 0.017 min-1 and 0.072 +/- 0.010 min-1 compared with 0.050 +/- 0.004 min-1, p less than 0.05) and correlated significantly with the rate-pressure product corrected for mean aortic valve gradient (r = 0.73, p = 0.0001) for all studies. However, analysis of patient subgroups demonstrated that this correlation held only for aortic stenosis (r = 0.79, p less than 0.005 for gradient-corrected rate-pressure product). Additionally, C-11 clearance was strongly correlated with the product of heart rate and mean wall stress in patients with aortic stenosis (r = 0.89, p less than 0.005) but not in patients with aortic regurgitation. Normalization of C-11 acetate clearance rate constants for gradient-corrected rate-pressure product were significantly lower in patients with loaded ventricles, particularly in the presence of a low ejection fraction, compared to normal subjects. Possible mechanisms include myocardial adaptation through hypertrophy or depressed contractility, which would both tend to reduce oxygen consumption under any given load. Serial comparison of C-11 acetate kinetics and noninvasive indexes of oxygen demand may provide assessment of disease progression in pathologic ventricular loading.