To quantify the changes in plasma concentrations of atracurium and laudanosine induced by the lack of hepatic function and circulation, the authors studied nine domestic pigs (22–25 kg) under-going an orthotopic liver transplantation, and three control animals without surgery, using atracurium as the muscle relaxant. After intubation facilitated by isoflurane 2–3%, anesthesia was maintained with isoflurane (0.5% in oxygen) and fentanyl (4 μg &OV0312; kg−1&OV0312; hr−1). Ventilation was controlled to keep end-tidal Co2at 35–40 mmHg, body temperature maintained at 35.5–37.5° C, and arterialpH at 7.35–7.50. The right sciatic nerve was stimulated with a nerve stimulator delivering a single twitch at 0.1 Hz with 0.2-ms duration, at supramaximal stimulation. The force of the corresponding evoked isometric muscle contraction was continuously measured by a force-displacement transducer. A single iv bolus of atracurium (2 mg/kg) was given to obtain a 90–95% twitch depression, followed 5 min later by a constant-rate iv infusion of atracurium at 120 μg &OV0312; kg−1&OV0312; min−1maintained during the entire investigation. Blood samples for plasma atracurium and laudanosine concentrations were drawn every 15 min. In the control group, plasma concentrations of atracurium remained stable between 6.5–8.0 μg/ml following initial bolus injection; plasma concentrations of laudanosine increased during the first 60 min, then remained stable between 0.69–0.74 μg/ml up to the end of the study. In animals undergoing transplantation, plasma concentrations of atracurium remained stable between 10–12 μg/ml, despite a 90-min duration of liver exclusion. In contrast, plasma concentrations of laudanosine were significantly increased 45 min after the hepatic vessels were clamped (from 0.57 ± 0.03 μg/ml to 0.91 ± 0.02 μg/ml, mean ± SE,P< 0.05), increased further to peak values of 1.24 ± 0.05 μg/ml after 90 min, and remained at these elevated concentrations after restoration of circulation to the transplanted liver. The results of the present study demonstrate that in pigs plasma clearance of atracurium does not depend on hepatic function. In contrast, plasma clearance of its major metabolite laudanosine is strongly dependent on liver function.