The effects of atrial pacing on tissue metabolite levels known to be sensitive to ischemia were examined. Anesthetized dogs were thoracotomized and a pacing electrode was sutured to the right atrium. Pacing at rates of 200 or 250 beats/min (10 animals per group) was performed for 15 min after base-line hemodynamic data had been obtained. At the end of the pacing period, a transmural biopsy was taken, frozen in liquid nitrogen, and sectioned into subepicardial, midmyocardial, and subendocardial layers. ATP, phosphocreatine, lactate, and glycogen were extracted and analyzed. Significant (P less than 0.001) transmural gradients of each of these metabolites existed in the control group. Pacing had no significant (P greater than 0.2) effect on any metabolite from layer to layer at 200 or 250 beats/min. However, indices of heart work (i.e., contractility (dP/dt), stroke work, and stroke volume) demonstrated significant reductions (P less than 0.01) due to pacing, while circumflex artery blood flow increased more than twofold (P less than 0.001) at the highest rate. These data suggest that physiologic autoregulation occurred during pacing and protected the subendocardium from stress-induced ischemic insult.