In the present study, the compartmental organization of the nucleus accumbens was investigated by comparing the pattern of leu-enkephalin immunoreactivity with that of the opioid receptor ligand, naloxone, an established marker for the compartmental organization of the neostriatum. Both patterns have a nonhomogeneous, patch-like appearance throughout the rostrocaudal extent of the nucleus and show a good, mutual correspondence. In the core of the nucleus accumbens as well as in the border region between the nucleus accumbens and the caudate-putamen, leu-enkephalin-rich areas are in register with opioid receptor-dense areas. In the shell region the precise relationship between the enkephalin and the naloxone patterns could not be established. A comparison of the connectivity patterns and neurochemical characteristics of the opioid receptor-dense compartments in the nucleus accumbens with those in the caudate-putamen reveals major discrepancies between these two striatal subdivisions. We therefore conclude that, rather than a bicompartmental patch/striosome-matrix organization, the nucleus accumbens has a multicompartmental organization. (C) 1993 Wiley-Liss, Inc.