The effects of propofol, nitrous oxide, and/or isoflurane on efferent activity of sympathetic muscle nerve fibers (MSA) were studied using percutaneous microneurographic recordings from the peroneal nerve. Eight ASA Physical Status I patients (30–70 yr of age) scheduled for otorhinolaryngeal surgery entered the study. The effects of propofol (2–2.5 mg·kg-1· min-1) induction, tracheal intubation, and maintenance of anesthesia with isoflurane (0.3%, 0.6%, and 1.2% end-tidal concentrations) and/or 70% nitrous oxide were studied with respect to MSA, arterial blood pressure, heart rate, and indices of skin blood flow (laser doppler photometry and finger pulse plethysmography). Induction of anesthesia with propofol decreased MSA to 34 ± 2% (mean ± SEM) (P< 0.05), and subsequent tracheal intubation increased MSA rapidly to 151 ± 23% (P< 0.05) of the control level. Isoflurane administration both with and without nitrous oxide led to a decrease of MSA (P< 0.05). However, during nitrous oxide/isoflurane anesthesia (1.0 MAC) MSA was 76 ± 38% higher than when isoflurane was used alone, although this implied a decrease in anesthetic depth to 0.5 MAC. This indicates that nitrous oxide and isoflurane have opposite effects on sympathetic outflow. During undisturbed propofol, nitrous oxide, and/or isoflurane administration (up to 1.0 MAC), MSA retained its normal pulse synchronous pattern, indicating that modulation of sympathetic outflow from arterial baroreceptors was still present. Skin blood flow increased sevenfold to tenfold in association with propofol induction (P< 0.05) and was maintained at an 11− to 19-fold increase during nitrous oxide and/or isoflurane anesthesia, without any difference between the two anesthetics. The changes of skin blood flow were unrelated to MSA, indicating that sympathetic activity to the skin is functionally dissociated from that to muscle.