Due to the short duration of action of naloxone, late respiratory impairment may be anticipated when given for the reversal of opioid anesthesia. Nalbuphine, a mixed agonist-antagonist chemically related to naloxone has a longer duration of action. It therefore was considered to be of clinical interest in reversing fentanyl anesthesia related depression of respiratory drive. In an open study 15 patients (mean age 40 years) undergoing orthopedic surgery received nalbuphine (0.1 mg/kg) after fentanyl (median dose 1.4 mg over a mean length of operation time of 95 min) - N2O/O2-anesthesia. 5, 15, 30, 45 and 60 min after nalbuphine, the ventilatory response to CO2-stimulation (rebreathing technique), was assessed and compared to control pre-anesthetic values. Nalbuphine reversed total apnoea due to fentanyl anesthesia. The slope of the CO2-response curve (sensitivity of the respiratory center to CO2) was -8% below control at the 5th and +13.5% and +22.6% at the 30th respectively 45th minute post nalbuphine. The ventilatory response to an increased end-tidal pCO2 of 60 mm Hg (level of response of the respiratory center to CO2) remained below control (-23.5% to -21%) over the following 60 minutes. A return of respiratory depression was not observed as the slope of the CO2-response curve remained above control values. From this study it was concluded that nalbuphine seemed to be a suitable compound for the reversal of opioid-anesthesia induced respiratory depression.