The effects of the active ingredient of Cannabis, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), and of the highly addictive drug heroin on in vivo dopamine transmission in the nucleus accumbens were compared in Sprague-Dawley rats by brain microdialysis, Delta(9)-THC and heroin increased extracellular dopamine concentrations selectively in the shell of the nucleus accumbens; these effects were mimicked by the synthetic cannabinoid agonist WIN55212-2. SR141716A, an antagonist of central cannabinoid receptors, prevented the effects of Delta(9)-THC but not those of heroin. Naloxone, a generic opioid antagonist, administered systemically, or naloxonazine, an antagonist of mu(1) opioid receptors, infused into the ventral tegmentum, prevented the action of cannabinoids and heroin on dopa mine transmission. Thus, Delta(9)-THC and heroin exert similar effects on mesolimbic dopamine transmission through a common mu(1) opioid receptor mechanism located in the ventral mesencephalic tegmentum.