The distribution of the inositol-1,4,5-trisphosphate (IP3) and the cardiac form of the ryanodine receptor, two intracellular calcium channels, was examined in the rat neostriatum. Both IP3 and ryanodine receptor labeling occurred within striatal medium spiny cells but only ryanodine receptor labeling was present in choline acetyltransferase- and parvalbumin-positive interneurons. IP3 receptor labeling was observed within cell bodies, dendrites and spines of spiny striatal neurons, as seen at both the light and electron microscopic levels. Subcellular labeling for the ryanodine receptor was restricted to cell bodies and proximal dendrites when a polyclonal antibody raised against a peptide sequence from the dog cardiac ryanodine receptor was employed. More extensive dendritic labeling was seen using monoclonal antibody MA3-916, also raised against the canine cardiac ryanodine receptor. At the ultrastructural level, labeled dendritic spines were observed frequently with the monoclonal but not the polyclonal antibody. Ryanodine receptor labeling also was present within astrocytic processes surrounding blood vessels and within the neuropil, regardless of the antibody used. The results of these studies suggest that the ryanodine receptor plays a general role in intracellular calcium regulation within striatal cells while the IP3 receptor plays a specialized role within spiny neurons.