The effects of 3.0 mg.kg-1 fentanyl on cerebral and peripheral hemodynamics alone and when combined with subanesthetic doses of pentobarbital (4.0 mg.kg-1), were studied in 11 unanesthetized, newborn lambs, in whom catheters had been previously inserted. After a control period, drugs were administered at 20-min intervals by intravenous bolus injection. Group 1 animals (n = 5) received fentanyl, pentobarbital, and naloxone (0.01 mg.kg-1), whereas Group 2 animals (n = 6) had the order of fentanyl and pentobarbital reversed. All animals responded to pain (withdrawal to tail clamping) and appeared conscious (eyes open, alert to sound) when either fentanyl or barbiturate was given alone. The combination of drugs, however, produced complete unresponsiveness. All of these effects were reversed by naloxone. Cardiac output did not change after either fentanyl or pentobarbital was administered individually but decreased significantly (29% in Group 1, 21% in Group 2) after administration of the combination of both. Mean arterial pressure and heart rate were unchanged. Cerebral blood flow, oxygen (O2) transport, and O2 consumption did not change after either administration of fentanyl or pentobarbital alone but decreased significantly after both (22%, 30%, 19%, respectively, in Group 1 and 35%, 40%, 38%, respectively, in Group 2). The decrease in cerebral O2 transport nearly paralleled the decrease in cerebral O2 consumption such that the ratio, the fractional O2 extraction, increased slightly. Fentanyl decreased kidney blood flow alone (24%) and in combination with pentobarbital (25%), although pentobarbital did so only when combined with fentanyl.(ABSTRACT TRUNCATED AT 250 WORDS)