BACKGROUND: Drugs of dependence cause dopamine release in the rat striatum. Human neuroimaging studies have shown an increase in dopamine in the equivalent region in response to stimulants and other drugs. AIMS: We tested whether opioids provoke dopamine release and its relationship to the subjective experience. METHOD: In two combined studies 14 heroin addicts on methadone maintenance treatment underwent two positron emission tomography brain scans of the dopamine system using [(11)C]-raclopride following an injection of placebo and either 50 mg intravenous diamorphine or 10 mg subcutaneous hydromorphone in a double-blind, random order design. RESULTS: Both opioids produced marked subjective and physiological effects, but no measurable change in [(11)C]-raclopride binding. CONCLUSIONS: The absence of a dopamine response to opioid agonists contrasts with that found with stimulant drugs and suggests dopamine may not play the same role in addiction to opioids. This questions the role of dopamine in the subjective experience of heroin in opioid addicts.