Cocaine is a potent sympathomimetic drug, and has been implicated as a causative factor in cardiac seizures. However, little is known about the effect of the drug on myocardial substrate utilization. In the present study, rats were injected intravenously with saline solution or one of three doses of cocaine-HCl (1.25, 5.0, 10.0 mg/kg) and subsequently rested or exercised (22 m/min at 15% grade) for 20 minutes. Hearts were removed and frozen within 30 seconds after the injection of anesthetic and within 10 seconds after opening the thoracic cavity. The mean values for resting glycogen content ranged from 24.9 to 27.0 mumol/g, and for glucose-6-phosphate, from 0.27 to 0.30 mumol/g across groups. These values were unaffected by cocaine or exercise. We conclude, based on the conditions of this study, that cocaine has no direct or indirect effect on glycogen storage of the myocardium at rest or during exercise.