In the striatum substance P (neurokinin-1) receptor, mRNA is selectively localized in large neurons that also express mRNA encoding choline acetyltransferase (ChAT) by in situ hybridization histochemistry. Substance P receptor mRNA is also localized in ChAT mRNA-containing neurons in the medial septum and basal forebrain cell groups. Thus, in the rat forebrain the substance P receptor appears to be expressed selectively by cholinergic neurons. Striatal neurons that contain substance P also utilize gamma-aminobutyric acid (GABA) as a transmitter. These neurons make synaptic contact with striatal cholinergic neurons, which are shown here to express the substance P receptor, and with other GABAergic neurons in the striatum and substantia nigra, which express GABA receptors but not substance P receptors. This suggests that individual striatal neurons may differentially affect target neurons dependent on the receptors expressed by those target neurons.