To determine whether acute elevation of plasma free fatty acids influences myocardial oxygen consumption in man, 17 patients underwent a metabolic study consisting of serial measurements of coronary sinus blood flow, heart rate and aortic blood pressure and arterial and coronary sinus determinations of oxygen, carbon dioxide, glycerol and free fatty acids both before and for 30 minutes after the intravenous administration of a bolus dose of 5,000 units of heparin. Of the 17 patients, 9 (group A) were fasting, and 8 (group B) ingested 100 g of fat 3 hours before the study in order to enhance post-heparin lipolysis. Marked elevation of arterial free fatty acid levels was seen in each group 30 minutes after administration of heparin (group A 713 ± 21 [mean ± standard error of the mean] to 1,757 ± 139 μmoles/liter, P < 0.001; group B 721 ± 57 to 2,668 ± 332 μmoles/liter, P < 0.001); significant increase in arterial-coronary sinus free fatty acid difference was also noted (group A 139 ± 11 to 298 ± 19 μmoles/liter, P < 0.001; group B 147 ± 11 to 334 ± 35 μmoles/liter, P < 0.001). Hemodynamic variables, including mean aortic pressure, heart rate, coronary sinus blood flow and coronary vascular resistance, were unchanged. Despite the marked increase in free fatty acids, myocardial oxygen consumption was unchanged 30 minutes after administration of heparin in both groups A and B. Myocardial triglyceride formation after heparin in both groups was suggested by (1) lack of change in cardiac respiratory quotient, (2) net myocardial glycerol uptake after heparin but not in the control state, and (3) oxygen extraction ratios totaling considerably in excess of 100 percent after heparin. The data suggest that acute elevation of plasma free fatty acids to pathophysiologic levels after heparin-induced lipolysis has no measurable effect on myocardial oxygen consumption in patients in stable condition, probably because the excess free fatty acids are stored as triglycerides rather than oxidized. © 1977.