Lidocaine infusions are used in several species to reduce anesthetic requirements and decrease the negative impact of high inhalant concentrations on the cardiorespiratory system. The objective of this study was to determine the effect of 2 dosages of lidocaine administered as constant rate infusions on isoflurane requirement (IR) in swine and to measure plasma concentrations of lidocaine and, its metabolite, monoethylglycinexylidide (MEGX) corresponding to IR. Six healthy commercial-bred pigs aged 74 ± 5.3 d and weighing 31.7 ± 5.4 kg were anesthetized and maintained with isoflurane during mechanical ventilation. Baseline IR was determined using a supramaximal mechanical stimulus on the dewclaw of the hind limb. After randomization for treatment allocation, lidocaine (loading dose; 2 mg/kg IV) was administered, followed by either 50 (CRI₅₀) or 200 (CRI₂₀₀) µg/kg/min and maintained for 30 min to reach a steady state and redetermination of IR. The study was repeated with the alternate infusion rate after a minimum washout period of 6 d. Lidocaine and MEGX plasma concentrations were quantified with HPLC and compared between groups. Heart rate, arterial blood pressure, end-tidal partial pressure of carbon dioxide, body temperature, and time to extubation were measured and compared between treatment groups. Baseline IR was 1.77% ± 0.34%. In pigs receiving CRI₅₀ (1.53%) and CRI₂₀₀ (1.61%), IR was lower than baseline IR, with a sparing effect of 7.8% (P = 0.046) and 13.4% (P = 0.041), respectively. Plasma concentrations of MEGX were inversely correlated to IR in pigs receiving CRI₅₀ but not CRI_200. Cardiovascular variables did not differ between treatments. Time to extubation was similar between groups (P = 0.92), 10.2 ± 4.5 min in subjects receiving CRI₅₀ and 11 ± 3.6 min in pigs receiving CRI₂₀₀. Infusion of lidocaine produced a nonlinear sparing effect on isoflurane requirement without appreciable, clinically relevant changes in cardiovascular variables or extubation time.