Smoking "crack" is currently popular; this results in rapidly peaking, high blood levels of cocaine. Our purpose was to investigate the effects of rapid cocaine administration. Hemodynamics, myocardial blood flow, and left ventricular cavity end-systolic and end-diastolic areas were measured in pentobarbital-anesthetized dogs before and 15 minutes after (1) a bolus intravenous injection of cocaine (n = 6), or (2) a 10-minute infusion of cocaine (n = 6), or (3) saline (n = 6) administration. In both treated groups cocaine caused a significant reduction in heart rate and left ventricular dP/dt compared with baseline measurements, and an increase in left ventricular end-diastolic pressure. Cocaine also caused dilation of the left ventricle and a fall in regional myocardial blood flow. In nine other dogs, proximal circumflex artery diameter, assessed by angiography, and regional myocardial blood flow were measured before and 3 to 5 minutes after cocaine (n = 7) or saline (n = 2). In treated animals, circumflex artery diameter was reduced 15 +/- 4% (range 2% to 29%, p less than 0.01 versus baseline) after cocaine. We conclude that in this model, rapid administration of cocaine depresses left ventricular function, causes left ventricular dilation, and is associated with coronary artery vasoconstriction and reduced myocardial blood flow.