Sufentanyl is a new, potent, short-acting, fentanyl-like morphinomimetic. In the present study we compared the effects of high doses of sufentanyl and morphine on the peripheral circulation in beta-blocked dogs. Skeletal muscle surface pH (m-pH) was recorded continuously as an index of the microcirculation. Sufentanyl (0.01 mg/kg) had no adverse effects on the peripheral perfusion. Morphine (4 mg/kg) caused a severe and rapid fall in m-pH from 7.34 to 7.14 during the 30-min experimental period. At the same time calculated blood volume decreased by 20%. This hypovolemic deterioration of the circulation was probably caused by a histamine-mediated increase in capillary pressure and filtration of plasma from the intravascular space to the interstitial space. As sufentanyl could be safely administered to beta-blocked dogs, we recommend human studies. On the other hand, we discourage the use of high-dose morphine anesthesia until human studies have proved that the collapse of the peripheral perfusion seen in this study is species specific.