Although altered effects of various anesthetics have been demonstrated during pregnancy, published studies have incompletely defined potential pregnancy-induced changes in the central nervous system toxicity of lidocaine. Accordingly, the seizure threshold for lidocaine was measured in three groups of mechanically ventilated rats breathing 70% N2O-30% O2: male (n = 21), nonpregnant female (n = 19), and pregnant female (n = 23). Lidocaine was administered intravenously at a constant rate of 2.3 mg·kg-1·min-1 while the electroencephalogram was monitored continuously. Total doses of lidocaine and the durations of lidocaine infusion necessary to induce seizure activity were similar among groups. Plasma lidocaine concentrations at the onset of electroencephalographic seizure activity were also similar among groups (male = 10.7 ± 5.5, nonpregnant female = 12.1 ± 4.9, pregnant female = 10.8 ± 4.1 μg/mL). In a subset of each group, brain lidocaine concentrations at the onset of seizure activity were also measured, and again no differences among groups were observed (male = 17.4 ± 6.3, nonpregnant female = 16.8 ± 4.5, pregnant female = 16.7 ± 4.2 μg/100 g wet wt). The authors conclude that there are no pregnancy-specific alterations in either plasma or brain concentration thresholds for central nervous system toxicity of lidocaine in rats.