The aims of this study were: (1) to measure noninvasively and near simultaneously myocardial blood flow, oxygen consumption, and contractile function and (2) to analyze myocardial energy expenditure and efficiency at rest and during dobutamine stress in normal humans. Dynamic and gated carbon-11 acetate positron emission tomography (PET) imaging was performed in 11 normal subjects. The initial uptake of (11)C-acetate was measured to estimate myocardial blood flow. Oxygen consumption was derived from the monoexponential slope of the (11)C-clearance curve recorded during myocardial washout. ECG-gated systolic and diastolic images were acquired during the peak myocardial (11)C activity to measure left ventricular radius, myocardial wall thickness, and long axis length. Myocardial oxygen consumption and parameters of cardiac geometry were used to determine myocardial energetics and cardiac efficiency by tension-area area analysis. Myocardial blood flow averaged 0. 8+/-0.06 ml min(-1) g(-1) at rest and 1.48+/-0.15 ml min(-1) g(-1) during dobutamine stress. Oxygen delivery and consumption were 151+/-13 and 88+/-15 microl O(2) min(-1) g(-1) at rest and increased to 291+/-31 and 216+/-31 microl O(2) min(-1) g(-1), respectively, during pharmacological stress (P<0.001). Oxygen extraction increased from 59%+/-8% at rest to 76%+/-9% during stress (P<0.001). Mechanical efficiency was 29%+/-6% at rest and 32%+/-6% during dobutamine stress (P=NS) while external work efficiency was 16%+/-6% at rest and increased to 21%+/-4% (P<0.01) during dobutamine stress. Stepwise linear regression analysis identified rate-pressure product and external cardiac work as major correlates of oxygen consumption. In summary, rapid dynamic and gated PET (11)C acetate imaging provides the unique capability to study noninvasively determinants of myocardial energy delivery, expenditure, and efficiency.