The hypotension accompanying isoflurane suggests that the anesthetic produces an attenuation of sympathetic tone. Previous studies examining the effects of isoflurane on sympathetic efferent nerve activity have required concomitant use of a basal anesthetic or decerebration, both of which independently alter sympathetic activity. This study was performed to examine the effects of isoflurane on sympathetic efferent nerve activity in the absence of basal anesthetic or decerebration. Five mongrel dogs were anesthetized with 4% isoflurane by mask. Platinum electrodes chronically were implanted around a renal nerve adjacent to the renal artery in order to measure renal sympathetic efferent nerve activity in the conscious and anesthetized animal. After 5–24 h for recovery, renal nerve activity and arterial pressure (via an implanted femoral artery cannula) were measured in the conscious, resting animal (control); during induction (4% isoflurane) and intubation; in the anesthetized animal (1.5% and 2.5% isoflurane); and during recovery and extubation.Isoflurane produced a significant dose-dependent depression of arterial blood pressure but did not significantly change heart rate from control. Renal sympathetic efferent nerve activity at 1.5% isoflurane was not significantly different from that in conscious animals, but nerve activity at 2.5% isoflurane was depressed significantly from both control and 1.5% isoflurane. Both intubation and extubation were accompanied by an increase in sympathetic nerve activity. Isoflurane appeared to directly depress sympathetic activity at both levels of anesthesia, but the direct depression of activity at 1.5% isoflurane seemed to be countered by reflex increases in sympathetic tone due to the hypotension accompanying the anesthesia. At 2.5% isoflurane, the central depression of reflex activity by isoflurane combined with direct depression of sympathetic efferent activity resulted in the attenuation of renal nerve activity.