The pharmacokinetics of sufentanil were determined in eight obese (94.1 +/- 14 kg, mean +/- SD) and eight control patients (70.1 +/- 13 kg) anesthetized for neurosurgery. After induction of anesthesia, 4-mu-g/kg of sufentanil was administrated in a single intravenous bolus. Multiple arterial samples were obtained at timed intervals over 6 h, and plasma concentrations of sufentanil were measured by radioimmunoassay. Calculation of pharmacokinetic variables from the derived compartmental models demonstrated an increased volume of distribution of sufentanil in the obese (9098 +/- 2793 mL/kg ideal body weight, mean +/- SD) when compared with a control group (5073 +/- 1673 mL/kg ideal body weight) (P < 0.01) and a prolonged elimination half-life (208 +/- 82 min vs 135 +/- 42 min, P < 0.05). The total volume of distribution correlated linearly with the degree of obesity, as expressed in percent ideal body weight (r = 0.67). In contrast, plasma clearance was similar in both obese and control groups (32.9 +/- 12.5 vs 26.4 +/- 5.7 mL/kg ideal body weight). The high lipid solubility of sufentanil probably explains the altered pharmacokinetics of this opioid in obese patients.