Lidocaine decreases the minimum alveolar concentration (MAC) of inhaled anesthetics and has been used clinically to reduce the requirements for other anesthetic drugs. In this study we examined the effects of lidocaine on isoflurane MAC in cats. Six cats were studied. In Experiment 1, the MAC of isoflurane was determined. An IV bolus of lidocaine 2 mg/kg was then administrated and venous plasma lidocaine concentrations were measured to determine pharmacokinetic values. In Experiment 2, lidocaine was administered to achieve target plasma concentrations between 1 and 11 mug/mL and the MAC of isoflurane was determined at each lidocaine plasma concentration. Actual lidocaine plasma concentrations were 1.06 +/- 0.12, 2.83 +/- 0.39, 4.93 +/- 0.64, 6.86 0.97, 8.86 2.10, and 9.84 +/- 1.34 mug/mL for the target concentrations of 1, 3, 5, 7, 9, and 11 mug/mL, respectively. The MAC of isoflurane in this study was 2.21% +/- 0.17%, 2.14% +/- 0.14%, 1.88% +/- 0.18%, 1.66% +/- 0.16%, 1.47% +/- 0.13%, 1.33% +/- 0.23%, and 1.06% +/- 0.19% at lidocaine target plasma concentrations of 0, 1, 3, 5, 7, 9, and 11 mug/mL, respectively. Lidocaine, at target plasma concentrations of 1, 3, 5, 7, 9, and 11 mug/mL, linearly decreased isoflurane MAC by -6% to 6%, 7% to 28%, 19% to 35%, 28% to 45%, 29% to 53%, and 44% to 59%, respectively. We conclude that lidocaine decreases the MAC of isoflurane.