The relationship of myocardial O2 consumption (MVO2) to its potential hemodynamic and mechanical determinants was investigated in eight healthy normal volunteers at rest and during infusion of dobutamine (5-10 micrograms.kg-1.min-1). MVO2 was calculated from the monoexponential myocardial clearance of [1-11C]acetate with positron emission tomography, and left ventricular mechanical function was assessed by two-dimensional echocardiography. Infusion of dobutamine increased heart rate by 53%, the tension-time index by 31%, and the rate-pressure product by 116%. Cardiac output (+70%), left ventricular ejection fraction (+24%), total mechanical energy [systolic pressure-volume area, (PVA) +84%], and left ventricular pressure-work index (+100%) also increased during infusion of dobutamine. During infusion of dobutamine, MVO2 increased from 96 +/- 17 to 233 +/- 19 J.min-1.100 g left ventricle-1, while myocardial efficiency (the ratio of PVA to MVO2) decreased from 46 +/- 8 to 35 +/- 4% (P < 0.001 each). MVO2 was best correlated (P < 0.001) with the PVA (r = 0.92) and the pressure-work index (r = 0.92). Infusion of dobutamine also resulted in a significant parallel upward shift of the PVA-MVO2 relationship, indicative of an increase in PVA-independent MVO2. Our data indicate that, in human subjects, MVO2 is mainly related to systolic PVA and that inotropic stimulation with dobutamine results in decreased efficiency of contraction, such as that previously described in isolated hearts.