Pregnant sheep are more vulnerable to the toxic effects of bupivacaine, a potent local anesthetic, than are nonpregnant sheep. In contrast, ovine pregnancy does not enhance the toxicity of mepivacaine, a drug with properties similar to lidocaine. We studied the central nervous and cardiovascular toxicity of lidocaine in pregnant sheep receiving a continuous intravenous drug infusion at the rate of 2 mg/kg/min and compared our results with data previously obtained in nonpregnant ewes. In all animals, toxic manifestations occurred in the following sequence: convulsions, hypotension, respiratory arrest, and circulatory collapse. The doses of lidocaine required to produce these symptoms in pregnant and nonpregnant ewes were similar. Convulsions occurred at 5.9 +/- 0.6 mg/kg (mean +/- SE) in the pregnant ewe and 5.8 +/- 1.8 mg/kg in the nonpregnant ewe, whereas circulatory collapse occurred at 40.7 +/- 2.6 and 36.7 +/- 3.3 mg/kg in the pregnant and nonpregnant animals, respectively. Lidocaine plasma concentrations associated with the onset of convulsions in both pregnant and nonpregnant ewes were almost identical (12.1 +/- 0.7 and 11.7 +/- 2.0 micrograms/ml, respectively). At circulatory collapse, these concentrations were 35.1 +/- 3.2 and 41.2 +/- 6.7 micrograms/ml, respectively. It appears that pregnancy does not enhance the toxic effects of lidocaine. These findings are similar to those for mepivacaine but not for bupivacaine, and may be related in part to differences in the way pregnancy affects serum protein binding of these drugs.