Myocardial extraction of free fatty acids (FFA), together with glucose, lactate, pyruvate, glycerol and oxygen was determined by simultaneous sampling of blood from an artery (a) and the coronary sinus (cs) at rest and during chest pains induced by atrial pacing in seven fasting male patients with ischaemic heart disease. Results were compared to those, at rest and during pacing at heart rate 140 beats min-1, in ten healthy men of similar age. A continuous i.v. infusion of 14C oleate and 3H palmitate enabled the calculation of simultaneous myocardial uptake and release of FFA as well as of the fraction of extracted FFA which underwent direct oxidation. During chest pain lactate net extraction decreased to become, in some patients, negative. FFA extraction, as estimated from the fractional extraction of labelled fatty acid was likewise decreased, while the a-cs O2 difference was not significantly altered. The fractional oxidation of extracted FFA was increased, whereas the calculated fatty acid release from the heart was unaltered. The increase in fractional oxidation was quantitatively correlated with the decrease in lactate extraction suggesting that it was related to the degree or extent of ischaemia. It was also proportional to the decrease in FFA extraction. Thus, in patients with angina pectoris the ischaemic myocardium may be subjected to a limitation not only with regard to oxygen but also substrate flux into the myocardial cells.