The effects of naltrexone-precipitated withdrawal from buprenorphine on behavior and regional cerebral blood flow (rCBF) were studied in 11 opiate-dependent patients. Patients initially received buprenorphine, 2 mg sublingually, every day for 7 days. They were then challenged sequentially with placebo and naltrexone, 25 mg orally, before single photon emission computed tomography with technetium-99m-d,l-hexamethyl-propylene amine oxime as tracer. Behavioral ratings of withdrawal severity were made before and after naltrexone/placebo administration. Naltrexone produced significantly greater signs and symptoms of opiate withdrawal than placebo. Analysis of variance revealed no significant regionally specific effect of naltrexone on rCBF ratios. Severity of withdrawal, however, showed a significant negative correlation with rCBF in the anterior cingulate cortex following naltrexone. These results are interesting as the anterior cingulate region has been implicated in the emotional component of pain and in opiate-induced analgesia.