Although epinephrine has been shown to improve myocardial blood flow during cardiopulmonary resuscitation (CPR), the effects of standard as well as larger doses of epinephrine on regional myocardial blood flow have not been examined. In this study we compared the effects of various doses of epinephrine on regional myocardial blood flow after a 10 min arrest in a swine preparation. Fifteen swine weighing greater than 15 kg each were instrumented for regional myocardial blood flow measurements with tracer microspheres. Regional blood flow was measured during normal sinus rhythm. After 10 min of ventricular fibrillation, CPR was begun and regional myocardial blood flow was determined. Animals were then randomly assigned to receive 0.02, 0.2, or 2.0 mg/kg epinephrine by peripheral injection. One minute after drug administration, regional myocardial blood flow measurements were repeated. The adjusted regional myocardial blood flows (ml/min/100 g) for animals given 0.02, 0.2, and 2.0 mg/kg epinephrine, respectively, were as follows: left atrium, 0.9, 67.4, and 58.8; right atrium, 0.3, 46.2, and 38.5; right ventricle, 0.7, 82.3, and 66.9; right interventricular septum, 1.7, 125.5, and 99.1; left interventricular septum, 2.8, 182.8, 109.5; mesointerventricular septum, 16.8, 142.2, and 79.2; left ventricular epicardium, 19.2, 98.5 and 108.7; left ventricular mesocardium, 22.8, 135.0, and 115.8; and left ventricular endocardium, 2.5, 176.1, and 132.9). All comparisons between the groups receiving 0.02 and 0.2 mg/kg epinephrine were statistically significant (p < .05). Comparisons between the groups receiving 0.02 and 2.0 mg/kg epinephrine were also statistically significant except for the right ventricle, right interventricular septum, left interventricular septum, and mesointerventricular septum. No statistically significant differences were noted for the animals receiving 0.2 and 2.0 mg/kg. This study suggests that epinephrine in doses larger than currently recommended during CPR is capable of improving regional myocardial blood flow over flows achieved with standard doses of epinephrine after a prolonged cardiac arrest. Circulation 75, No. 2, 491-497, 1987. EPINEPHRINE has been shown to improve regional myocardial blood flow during cardiac resuscition.'The optimal dose of epinephrine to be used during closed-chest cardiopulmonary resuscitation (CPR) to augment regional myocardial blood flow has not been determined. The present American Heart Association guidelines recommend a dose of 0.5 to 1.0 mg of epinephrine in adults.