The aim of this study is to characterize the regional and laminar distribution patterns of various neurotransmitter binding sites in areas 3a, 3b, 1, and 2 of the human primary somatosensory cortex, and to compare these receptor-based ''maps'' with the cytoarchitectonic parcelation. Cryostat sections from a dorsomedial region of the postcentral gyrus close to the interhemispheric fissure and from a ventrolateral region close to the Sylvian fissure were examined. Neurotransmitter-binding sites were analyzed with quantitative in vitro receptor autoradiography. Different muscarinic-binding sites were labeled with [H-3]pirenzepine and [H-3]oxotremorine-M, noradrenergic-binding sites with [H-3]prazosin, different serotoninergic-binding sites with [H-3]5-hydroxytryptamine and [H-3]ketanserine, glutamate-binding sites with L-[H-3]glutamate, and GABA-binding sites with [H-3]muscimol. Adjacent sections were stained with a modified Nissl method for cytoarchitectonic analysis. The binding sites either were preferentially localized in the superficial layers ([H-3]5-hydroxytryptamine, [H-3]prazosin, L-[H-3]glutamate, [H-3]muscimol, and [H-3]pirenzepine) or were more homogeneously distributed with highest densities in layers III-V ([H-3]oxotremorine-M and [H-3]ketanserine). Changes in the distribution patterns of [H-3]oxotremorine-M- and [H-3]ketanserine-binding sites precisely matched the borders between areas 4/3a, 3b/1, and 1/2, as defined cytoarchitectionically. In addition, the autoradiographs showed that area 1 possibly consists of two subregions which cannot be distinguished cytoarchitectonically. The results demonstrate that the regional and laminar distribution patterns of some, but not all, transmitter-binding sites are precisely correlated with the cytoarchitectonic parcelation of the human primary somatosensory cortex. In addition, binding sites may reveal new borders not detectable in Nissl-stained sections. Finally the human primary somatosensory cortex differs clearly from the primary motor cortex due to higher densities of L-[H-3]glutamate-, [H-3]muscimol-, [H-3]pirenzepine-, [H-3]oxotremorine-M-, and [H-3]ketanserine-binding sites. (C) 1997 Academic Press.