This study evaluated the relationship between the sympathetic withdrawal response and increases in spontaneous ventilation during naltrexone treatment in opioid-dependent patients. Naltrexone was given in repeated increasing doses by orogastric tube to 16 opioid-dependent patients during propofol anesthesia. Sympathetic activity was evaluated in 64-second segments by low frequency heart rate variability (0.02-0.10 Hz) and minute ventilation was measured every 15 minutes. During naltrexone treatment, heart rate and blood pressure increased with no change in the electroencephalogram as measured by the bispectral index. Sympathetic activity increased five-fold and minute ventilation increased by 50% during naltrexone administration. There was a significant correlation between the time of the peak sympathetic response and peak ventilation (r = 0.83, p < 0.001). In three control patients, who received anesthesia for surgery without naltrexone treatment, no increases in sympathetic or respiratory parameters were seen. These results indicate that peak sympathetic and respiratory stimulation occur together during opiate receptor antagonism in opioid addicts.