AbstractCytochrome oxidase (CO) activity was examined in the neostriatum of normal adult rats at the tight and electron microscopic level. At the light microscopic level a heterogeneous distribution of CO activity was observed and was characterized by patches of high activity ranging in size from 200 to 800 μm surrounded or adjacent to regions of lower activity. The most dorsomedial and ventromedial regions of the caudate nucleus appeared to be consistently high in activity in all animals. At the ultrastructural level CO reaction product was localized to the membranes and intracristal spaces of mitochondria. The most reactive mitochondria (those containing the densest precipitates of reaction product) were found within the dendrites of spiny neurons in all caudate regions. In areas of high CO activity the mitochondria within bundles of myelinated fibers and in many axon terminals were also highly reactive whereas those in neuronal somata, primary dendrites, and glial cells and processes exhibited relatively little activity.Quantitative study showed that mitochondria within dendrites accounted for most of the CO activity in caudate neuropil. The mitochondria within dendrites and axon terminals were more reactive in regions of high CO activity than in regions of low CO activity. No differences in the density of synapses or in the proportions of axospinous and axodendritic synapses were observed between CO‐rich and CO‐poor areas.Heterogeneity in the distribution of CO activity in the caudate nucleus may be related to the “patchy” pattern of localization previously observed for some neostriatal afferents, enzymes, transmitters, peptides, and receptor ligands. Also the present results suggest that differences in metabolic activity between regions of the caudate nucleus may depend more on the relative frequency of neuronal discharge at individual synaptic sites than on the density of synapses present within a given area. The high metabolic demands of spiny dendrites as compared to other neuronal profiles in the neostriatum may reflect their level of synaptic activity, since spines are known to participate in the majority of synapses in the caudate