In the present investigation the effect of elevated arterial free fatty acid (FFA) concentrations on regional myocardial blood flow (MBF), myocardial metabolism and hemodynamics during ischemia was studied in anesthetized dogs. Ischemia was induced by stenosis of the left interventricular coronary artery. Mean poststenotic coronary artery pressure was kept constant during ischemia. FFA concentrations were elevated by intravenous injection of heparin (group I), intralipid (group II) or both substances (group III). After elevation of FFA concentrations by heparin alone or together with intralipid, heart rate gradually increased, while aortic pressure tended to decrease. Slight elevation of arterial FFA levels (up to 0.30 mM, group I, and up to 0.53 mM, group II) had no significant effect on total MBF and uptake of glucose, FFA, and oxygen or release of lactate in the ischemic myocardium. However, elevating arterial FFA levels up to 0.81 mM (Group III), significantly decreased total MBF (6%), endo/epicardial blood flow ratio (13%), and oxygen uptake (34%) in the ischemic myocardium and resulted in release of lactate from this area. The release of potassium, inorganic phosphate and H+ as well as plasma CO2 concentration were not influenced. Neither was the uptake of glucose and FFA. These findings suggest that elevated arterial FFA concentrations can decrease MBF and augment lactate production in the ischemic myocardium.