The onset of conduction blockade in the vagus nerve of pregnant and nonpregnant rabbits was studied utilizing an in vitro sheath nerve preparation. The time required for 50% depression of the action potential (AP) of A, B, and C vagal fibers from five pregnant and six nonpregnant animals was determined after the application of bupivacaine (0.35 mM). The onset of conduction block occurred in 6.7-12.1 min in the A, B, and C fibers from pregnant animals compared to onset times of 17.9-31.6 min in nerves taken from nonpregnant rabbits. The difference in onset time for each type of nerve fiber from pregnant and nonpregnant animals was highly significant. The results suggest either an increased sensitivity of nerve fibers from pregnant animals to bupivacaine or an enhanced diffusion of the bupivacaine to the membrane receptor site. Mechanical factors are clearly not responsible for the observed results. Hormonal factors may play a role in the decreased anesthetic latency, because progesterone levels were significantly higher in the pregnant animals.