This study explored the effectiveness of oral clonidine premedication in attenuating sympathetic activation, tachycardia, and hypertension triggered by desflurane. After institutional review board approval, informed consent was obtained from 15 young, healthy male volunteers. Heart rate (HR, electrocardiogram), mean arterial pressure (MAP, radial artery catheter), and central venous pressure (CVP, jugular vein) were monitored. Recordings of sympathetic nerve activity (SNA) were obtained from the peroneal nerve via percutaneously placed tungsten needles. After baseline recordings, subjects were randomized to receive either a placebo (n = 10) or 0.3 mg of clonidine (n = 9) per os (PO). One hour later, repeat recordings were obtained. Propofol (2.5 mg/kg) and vecuronium (0.15 mg/kg) were given intravenously. Ventilation via a mask (100% O2) was used to maintain normocarbia. Two minutes after propofol administration, the desflurane vaporizer was set at 3.6% (0.5 minimum alveolar anesthetic concentration [MAC]) and increased at 1-min intervals to 7.2% and 11% (1.0 and 1.5 MAC). After 10 min, the trachea was intubated and 20 min later steady-state neurocirculatory recordings were obtained at 5.4%, during the first 5 min after advancing the vaporizer from 5.4% to 11% ("transition"), and at 11%. Resting HR, MAP, and SNA were similar between the two groups. PO clonidine reduced SNA, CVP, and MAP but did not change HR. In both groups propofol decreased SNA and MAP, and increased HR. The administration of desflurane via a mask resulted in significant increases in SNA, HR, and MAP. Clonidine reduced the HR and MAP responses by approximately 30%-40% during induction and transition periods.(ABSTRACT TRUNCATED AT 250 WORDS)