BACKGROUND The ability of opioids to produce complete general anesthesia is controversial. Nitrous oxide (N2O) is often added to fentanyl-based anesthetics to produce unconsciousness and amnesia. The addition of N2O may adversely affects fentanyl's hemodynamic stability and safety. The purpose of this study was to determine the physiologic consequences of combining N2O with fentanyl in newborn animals. METHODS The effects of 50% nitrous oxide in oxygen (O2), and 50% N2O in O2 combined with 3,000 micrograms/kg fentanyl, on cerebral and peripheral hemodynamics were studied in seven unanesthetized newborn lambs, in whom catheters were previously inserted. After a control period, lambs were placed in a hood in which inspired gas concentrations were controlled and which minimized external stimuli. After 30 min of breathing room air, the lambs breathed 50% N2O in O2 for an additional 30 min. The lambs were then given 3,000 micrograms/kg fentanyl by intravenous bolus and by infusion (1,000 micrograms.kg-1 x h-1) for 60 min while continuing to breathe 50% N2O in O2. RESULTS All animals responded to pain (tail clamp) and alerted to sound when breathing room air or when N2O was used alone. Adding fentanyl to the N2O abolished all responses to pain, but not to sound. Additionally, fentanyl produced immediate apnea necessitating tracheal intubation and mechanical ventilation. Mean arterial pressure and heart rate increased 27% and 23%, respectively, after fentanyl administration, intubation, and ventilation. It did not change over the course of the fentanyl infusion. Cerebral blood flow, O2 consumption, and O2 delivery did not change when N2O was administered alone or in combination with fentanyl. Splanchnic blood flow was unaffected by treatment over time. Renal blood flow decreased by 21% after fentanyl administration, but was unaffected by N2O alone. Right and left ventricular blood flow increased (47% and 26%, respectively) after fentanyl administration, intubation, and ventilation, but not when N2O was administered alone. CONCLUSIONS Fentanyl (3,000 micrograms/kg) when combined with 50% N2O in O2 produced a plane of general anesthesia in newborn lambs in which the behavioral responses to painful stimuli were abolished. The response to sound was never eliminated, nor was cerebral oxygen consumption decreased. The combination of 50% N2O in O2, 3,000 micrograms/kg fentanyl, tracheal intubation, and mechanical ventilation did not depress heart rate, blood pressure, or blood flow to any of the major organs, except the kidneys.