Changes in opioid neurotransmission have been implicated in several basal ganglia-related neurological and psychiatric disorders. To gain a better insight into the opioid receptor distribution in the normal human striatum, we examined in post mortem brain the distribution of the mu opioid receptor using ligand binding of [3H]O-ala2-N-methyl-phe4, gly-ol5-enkephalin. Our results indicate at the regional level the presence of a dorsal-to-ventral high-to-low density gradient in the striatum, with lowest densities in the ventral one-third of the putamen and in the nucleus accumbens. At the subregional level, the nucleus accumbens shows two major types of heterogeneities. First, low vs intermediate binding densities distinguish the core and shell subdivisions, respectively. The low-density core and intermediate-density shell regions extend into the putamen and are therefore characteristic for the entire ventral striatum. The second type of heterogeneity is formed by small areas located along the ventral contours of the nucleus accumbens and putamen that display the highest binding density of the entire striatum. Since these areas can also be recognized in the distribution patterns of other markers and in the cytoarchitecture, they appear to possess a separate identity. To emphasize their special neurochemical characteristics we propose the description "neurochemically unique domains in the accumbens and putamen". The present results, with the difference between core and shell of the ventral striatum as the most prominent outcome, together with the notion that the connectional relationships and neurochemical organization of the striatum are very heterogeneous, suggest a strong regional functional differentiation for mu receptor function in the human striatum.