It has been shown that rapid opioid detoxification is associated with increased sympathetic activity (SYMP) and plasma catecholamines. Heart rate (HR) variability may provide a noninvasive method of evaluating withdrawal and sympathetic activation caused by the reversal of opioid binding in patients who are opioid dependent. The purpose of this study was to evaluate the relationship between HR variability and plasma catecholamines during opioid detoxification. Patients were anesthetized with propofol, intubated, paralyzed with rocuronium infusion, and ventilated. The bispectral index (BIS) of the electroencephalogram was recorded with the patient awake as well as during propofol anesthesia. SYMP was determined by power spectral analysis of HR variability. Plasma epinephrine and norepinephrine were measured at baseline propofol anesthesia and during naltrexone treatment in eight opioid-dependent patients. Nonopioid-dependent controls (n = 7) were monitored during surgery without naltrexone treatment or measurement of plasma catecholamines. Compared with an awake status, propofol anesthesia significantly decreased the BIS and SYMP in both groups of patients. Controls showed no change from baseline anesthetized levels during surgery. Plasma norepinephrine and epinephrine as well as SYMP increased 300 to 400% (P < .05) during naltrexone treatment in opioid-dependent patients, and the time to peak increase in plasma norepinephrine correlated with the increase in SYMP (r = 0.89, P < .01). These results confirm that opioid detoxification increases plasma catecholamines and SYMP in a similar manner. HR rate variability may provide a low-cost real-time noninvasive method of evaluating the reversal of opioid binding in opioid-dependent patients.