The relative central nervous system and cardiovascular toxicity of bupivacaine was compared in pregnant and nonpregnant ewes during continuous infusion of bupivacaine into the jugular vein at the rate of 0.5 mg X kg-1 X min-1. In all animals, identical symptoms of toxicity occurred in the following order: convulsions, hypotension, respiratory arrest, and circulatory collapse. The dose of bupivacaine required to produce central nervous system (CNS) toxicity in the pregnant ewe tended to be lower than in the nonpregnant animal, although the difference was not statistically significant (P less than 0.1). However, the mean dose of bupivacaine resulting in cardiovascular collapse was significantly lower in pregnant ewes (5.1 +/- 0.7 mg/kg) than in nonpregnant animals (8.9 +/- 0.9 mg/kg). Similarly, bupivacaine blood concentrations at the onset of respiratory arrest and circulatory collapse were lower in the pregnant group, being 5.2 +/- 0.7 micrograms/ml and 5.5 +/- 0.8 micrograms/ml, respectively, versus 7.5 +/- 1.0 microgram/ml and 8.0 +/- 0.9 micrograms/ml, respectively, in the nonpregnant group (P less than 0.05). The concentration of bupivacaine in the brain of pregnant ewes at the time of cardiovascular collapse was significantly lower (P less than 0.01) than in the nonpregnant group (7.5 +/- 1.5 vs. 16.3 +/- 1.7 micrograms/g). The myocardial tissue concentration of bupivacaine also tended to be lower in the pregnant group, although the differences were not statistically significant (P less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)