A widespread distribution of dopamine D 1 receptors in the neocortex is well recognized. However, the presence of dopamine D 2 receptors in this structure has only recently been established [Martres et al. (1985) Eur. J. Pharmac. 118, 211–219; Lidow et al. (1989) Proc. natn. Acad. Sci. U.S.A. 86, 6412–6416]. In the present paper, a highly specific antagonist, [ 3H]raclopride, was used for autoradiographic determination of the distribution of D 2 receptors in 12 cytoarchitectonic areas of the frontal, parietal, and occipital lobes of the rhesus monkey. A low density of D 2-specific [ 3H]raclopride binding (1.5–4.0 fmol/mg tissue) was detected in all layers of all cortical areas studied. Throughout the entire cortex, the highest density of binding was consistently found in layer V. This is a unique distribution not observed so far for any other neurotransmitter receptor subtype in monkey cerebral cortex, including D 1 receptor. In addition, a comparison was made of the distribution of [ 3H]raclopride and [ 3H]spiperone, which has been commonly used in previous attempts to label cortical D 2 receptors. We found marked differences in the distribution of these two radioligands. In the prefrontal cortex, the pattern of [ 3H]spiperone binding in the presence of ketanserin resembled the combined distribution of 5-HT ic serotoninergic and α 2-adrenergic sites as well as D 2 receptors. Thus, [ 3H]raclopride provides a better estimation of the D 2 receptor distribution than does [ 3H]spiperone. The distribution of D 2-specific binding of [ 3H]raclopride was also compared with the D 1-specific binding of [ 3H]SCH23390 in the presence of mianserin to block labeling to 5-HT 2 and 5-HT IC sites. The density of D 1-specific [ 3H]SCH23390 binding was 10–20 times higher than that of D 2-speciflc [ 3H]raclopride binding throughout the cortex. The densities of both [ 3H]raclopride and [ 3H]SCH23390 binding sites display a rostral-caudal gradient with the highest concentrations in prefrontal and the lowest concentrations in the occipital cortex. However, the binding sites of these two ligands had different laminar distributions in all areas examined. In contrast to preferential [ 3H]raclopride binding in layer V, a bilaminar pattern of [ 3H]SCH23390 labeling was observed in most cytoarchitectonic areas, with the highest concentrations in supragranular layers I, II and IIIa and infragranular layers V and VI. Whereas [ 3H]raclopride binding was similar in all cytoarchitectonic areas, [ 3H]SCH23390 exhibited some region-specific variations in the primary visual and motor cortex. The different regional and laminar distributions of D 1 and D 2 dopaminergic receptors indicates that they may subserve different aspects of dopamine function in the cerebral cortex.