The aim of this study was to make a comparison of brain structure between a group of opioid-dependent subjects and healthy controls. We report the results of an ;optimized' voxel-based morphometry study on a sample of nine opioid-dependent subjects with no comorbid substance misuse disorders versus 21 healthy controls. We found a significant reduction in grey matter volume of the thalamus after controlling for age and total grey matter volume. Regression analysis of substance use variables in the opioid-dependent sample shows that only level of alcohol use negatively predicts grey matter volume for this region of difference. We suggest that level of nondependent alcohol use could influence reduced thalamic grey matter volume in opioid-dependent subjects.