Arterio-coronary sinus (A-Cs) differences of plasma citrate, glucose, free fatty acids and blood lactate were measured in 19 patients with coronary artery disease (CAD) and in eight control subjects exposed to atrial pacing. Among patients with CAD 11 showed a myocardial release of lactate during pacing (lactate producers, LP) while myocardial lactate extraction was unchanged in the remaining eight patients (lactate non-producers, LNP). In patients with CAD, (A-Cs) plasma citrate differences became increasingly negative during recovery from pacing, values at rest and at 3-5 min of recovery were: -5 +/- 2 mumol/l (mean +/- SD) vs. -12 +/- 5 mumol/l in LP (P less than 0.001) and -6 +/- 3 mumol/l vs. -8 +/- 4 mumol/l in LNP (P less than 0.01). In controls, (A-Cs) citrate difference varied inversely, from -8 +/- 4 mumol/l at rest to -2 +/- 4 mumol/l at 3-5 min of recovery (P less than 0.001). An increasingly negative (A-Cs) plasma citrate difference during recovery from pacing-induced angina pectoris is suggested to reflect a wash-out of accumulated citrate from ischaemic heart cells; and is proposed as a more sensitive marker of ischaemia in man than a myocardial release of lactate.