Anginal threshold and cardiac metabolism during infusion of glucose, 350 mg/min, were compared with control values before, during, and after pacing in nine patients with coronary artery disease (CAD) and nine patients without coronary artery disease (non-CAD). Pacing induced no ischemia in non-CAD patients; in CAD patients, intolerable angina developed in less than 5 minutes. However, glucose infusion in the latter group increased the time to onset of angina (110 ± 24 seconds before infusion versus 140 ± 24 seconds following infusion) and decreased the extent of ST segment depression (1.8 ± 0.3 mm before infusion versus 0.9 ± 0.2 mm following infusion, p < 0.01) following pacing. In all subjects, arterial levels and cardiac uptake of glucose rose by 100% ( p < 0.001) and those of free fatty acids fell by 50% ( p < 0.01). Arterial lactate and uptake of lactate by nonischemic myocardium increased by 30% ( p < 0.05). During pacing in CAD patients, this elevated uptake was outweighed by similar increases of lactate release from ischemic areas, leaving mean negative global exchanges unaltered. In CAD patients solely, rebuilding of cardiac glycogen after pacing was suggested from augmented citrate efflux in the control period but not during glucose infusion, suggesting a glycogen-sparing effect. Arterial concentrations and net cardiac fluxes of oxygen, glutamate, and alanine remained unaltered. In conclusion, beneficial effects of glucose during ischemia are associated with increased aerobic and anaerobic glycolysis, saving of glycogen, and decreased lipolysis.