The aim of this study was to quantitate imidazoline receptors in postmortem brains of heroin addicts who died of an opiate overdose. The density of I2-imidazoline receptors ([3H]idazoxan binding in the presence of adrenaline) and the immunoreactivity of the related 29/30 kDa imidazoline receptor protein were decreased (39% and 28%, respectively) in the frontal cortex. The density of brain I2-imidazoline receptors was also decreased in heroin-dependent rats (27%). This novel finding indicates that opiate addiction induces down-regulation of I2-imidazoline receptors in astrocytes, and presumably down-regulation of the functions associated with these receptors.