To evaluate the role of the autonomic nervous system in the development of hypotension during air embolism, we studied the effects of an intravenous bolus injection of air (0.5 ml/kg) on mean blood pressure (MBP), central venous pressure (CVP), and renal nerve activity (RNA) in urethan-anesthetized rabbits of three groups: animals with an intact neuraxis (intact group; n = 5), cervical-vagotomized animals (vagotomy group; n = 5), and sinoaortic-denervated animals (SAD group; n = 5). In the intact group, despite a significant decrease in MBP at 10 s after air injection, RNA did not increase from the preinjection level. This response of RNA was associated with a significant increase in CVP and lasted for 20 s after the injection. Vagotomized animals, however, exhibited a significant augmentation in RNA in response to a drop in MBP at 10 s after the injection. In the SAD group, profound declines in both MBP and RNA were observed at 10 s after the injection of air. Animals in these two groups showed remarkable increases in CVP. At 5 min after the air administration, MBP in the vagotomy group was significantly higher than that in the intact group. All animals in the SAD group died within 5 min of the injection. These results indicate that during hypotension induced by air injection, sympathetic activation through arterial baroreceptors may be depressed by vagal afferents emanating from cardiopulmonary receptors; the results also suggest that the arterial baroreceptor nerves may be required to overcome the lethal events that should occur during venous air embolism.