OBJECTIVE To determine the pharmacokinetics of ketamine and norketamine in isoflurane-anesthetized dogs. Animals-6 dogs. METHODS The minimum alveolar concentration (MAC) of isoflurane was determined in each dog. Isoflurane concentration was then set at 0.75 times the individual's MAC, and ketamine (3 mg/kg) was administered IV. Blood samples were collected at various times following ketamine administration. Blood was immediately centrifuged, and the plasma separated and frozen until analyzed. Ketamine and norketamine concentrations were measured in the plasma samples by use of liquid chromatography-mass spectrometry. Ketamine concentration-time data were fitted to compartment models. Norketamine concentration-time data were examined by use of noncompartmental analysis. RESULTS The MAC of isoflurane was 1.43 +/- 0.18% (mean +/- SD). A 2-compartment model best described the disposition of ketamine. The apparent volume of distribution of the central compartment, the apparent volume of distribution at steady state, and the clearance were 371.3 +/- 162 mL/kg, 4,060.3 +/- 2,405.7 mL/kg, and 58.2 +/- 17.3 mL/min/kg, respectively. Norketamine rapidly appeared in plasma following ketamine administration and had a terminal half-life of 63.6 +/- 23.9 minutes. A large variability in plasma concentrations, and therefore pharmacokinetic parameters, was observed among dogs for ketamine and norketamine. CONCLUSIONS In isofluraneanesthetized dogs, a high variability in the disposition of ketamine appears to exist among individuals. The disposition of ketamine may be difficult to predict in clinical patients.