Replacement therapy with buprenorphine is clinically effective in reducing withdrawal and craving for heroin during detoxification but not in decreasing the probability of relapse after detoxification. This study examined the acute effects of buprenorphine on brain responses to heroin-related cues to reveal the neurobiological and therapeutic mechanisms of addiction and relapse. Fifteen heroin addicts at a very early period of abstinence, were studied in two separate periods 10-15 min apart: an early period (5-45 min) and a later period (60-105 min) after sublingual buprenorphine, roughly covering the onset and peak of buprenorphine plasma level. During both periods, fMRI scanning with heroin-related visual stimuli were performed followed by questionnaires. Under effect of buprenorphine, brain responses to heroin-related cues showed decrease in amygdala, hippocampus, ventral tegmental area (VTA) and thalamus but no changes in ventral striatum and orbital-prefrontal-parietal cortices. As an uncontrolled trial, these preliminary results suggest that buprenorphine has specific brain targets in reducing withdrawal and craving during early abstinence, and that ventral striatum and orbital-prefrontal-parietal cortices may be the key targets in developing therapy for drug addiction and relapse. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.