The response of the human peripheral circulation to morphine in large doses independent of cardiac and respiratory influences has not been delineated. In 28 patients during cardiopulmonary bypass, alterations of peripheral vascular resistance (PVR) and capacitance in response to rapid arterial injection of morphine, 0.5 mg/kg or 1 mg/kg alone, or preceded by promethazine, 1 mg/kg, naloxone, 10 μg/kg, or naloxone, 20 μg/kg, were recorded over 15 min at a constant perfusion rate. Both doses of morphine decreased PVR by 46 per cent at 2 min, with values returning to control at 9 min. When promethazine preceded morphine, the decrease in PVR after morphine was 25 per cent. Naloxone did not alter the response. An increase in capacitance of 600 ml observed 5 min after morphine administration did not revert to control after 15 min, and was unaltered by prior administration of naloxone.