Of the cloned P2X receptor subunits, six are expressed in sensory neurons, suggesting that the native channels may be heteromultimers with diverse composition. It has been proposed that P2X(2) and P2X(3) form heteromultimers in sensory neurons. We further tested this hypothesis by examining the relationship of P2X(2) and P2X(3) immunocytochemically. In rat dorsal root and nodose ganglia, P2X(2)- and P2X(3)-immunoreactivity (-ir) were highly colocalized, although single-labeled cells were also present. In dorsal. root ganglia (DRG), in some cases P2X(2)-ir appeared to be present in satellite cells. In dorsal horn of spinal cord, at low magnification the laminar localization of P2X(2)- and P2X(3)-ir overlapped, but at high magnification colocalization was rarely observed. In contrast, in the solitary tract and its nucleus (NTS), colocalization of P2X(2)- and P2X(3)-ir was seen at low and high magnification. These results suggest that the relationship of P2X(2)- and P2X(3)-ir is different in nodose and dorsal root ganglia and might reflect differences in the targeting of P2X receptors in different sensory neurons. In monkey, P2X(2)-ir was observed in DRG neurons and satellite cells and in dorsal horn of spinal cord. P2X(3)-ir was also seen in DRG neurons. However, the presence of P2X(2)-ir in NTS as well as the presence of P2X(3)-ir in spinal cord and NTS could not be established definitively. These results suggest species differences, although a more extensive study of primate sensory systems is necessary. (C) 1997 Published by Elsevier Science Ltd.