The influence of age and volatile anesthetic agents on plasma concentrations and toxic effects of bupivacaine were studied in 2-day-old, 2-week-old, and 2-month-old pigs. Bupivacaine was infused at a constant rate while the pigs' ECGs and EEGs were recorded. Six pigs in each age group were lightly anesthetized with 70% N2O/ 30% O2during the bupivacaine infusion, and twelve 2-day-old pigs were anesthetized with 70% N2O/30% O2plus either 0.5 × MAC halothane or isoflurane. Two-day-old pigs were more resistant than older pigs to the toxic effects of bupivacaine despite higher plasma concentrations at all sample times. All pigs given N2O alone or N2O plus halothane had ventricular dysrhythmias, but only one pig in the N2O plus isoflurane group had a ventricular dysrhythmia. Threshold doses of bupivacaine for dysrhythmias in the N2O alone and N2O plus halothane groups did not differ. Seizures occurred in all pigs in the N2O alone group, in none of the N2O plus halothane group, and in two of the N2O plus isoflurane group. The doses required to depress cardiac index and cause asystole were less in the groups receiving halothane and isoflurane. It was concluded that N2O plus halothane and N2O plus isoflurane increase the lethality of bupivacaine while preventing early warning signs of toxicity.