Animal studies indicate that oversupply of fatty acids derived from the action of cardiac lipoprotein lipase (LPL) on plasma lipoproteins may contribute to myocardial dysfunction. However, the contribution of circulating triglycerides to myocardial fatty acid supply in humans is not known. Six postabsorptive nondiabetic subjects who were scheduled for diagnostic coronary angiography were studied. (14)C oleate and a lipid emulsion labeled with (3)H triolein were infused to assess myocardial uptake of free fatty acids (FFAs) and triglycerides, as well as myocardial spillover of LPL-generated fatty acids. Six paired blood samples were taken from the femoral artery and the coronary sinus. Coronary sinus concentrations of unlabeled triglycerides were slightly, but not significantly, lower than arterial (P = 0.12), whereas labeled triglyceride concentrations were significantly lower in the coronary sinus than in the artery (P < 0.05; extraction fraction congruent with 11%). Triglycerides and FFAs accounted for approximately 17% and approximately 83%, respectively, of myocardial fatty acid uptake. Systemic and myocardial fractional spillover of LPL-generated fatty acids was 49.0 +/- 7% and 34.7 +/- 13%, respectively. The myocardium was a minor contributor to systemic triglyceride uptake ( approximately 3%) and a trivial contributor to systemic FFA production ( approximately 0.5%). These results indicate that circulating triglycerides may be a significant source of fatty acids for myocardial respiration.