Cytochrome oxidase was histochemically localized in the hippocampus and dentate gyrus of various species of mammals. The most intense staining was observed within stratum moleculare of areas CA1-3 and the outer molecular layer of the dentate gyrus, as well as the somatic and basal dendritic layers of CA3. These regions correspond to the synaptic terminal fields of major excitatory afferent pathways to the hippocampus. The somata of CA3 pyramidal cells and various interneurons were more intensely stained than CA1 pyramidal cells and dentate granule cells, and these levels appeared to correlate positively with their reported rates of spontaneous firing. At the electron-microscopic level, the highest concentrations of densely reactive mitochondria were localized within the distal apical dendritic profiles of principal cells (granule and pyramidal) and certain interneurons (pyramidal basket and stratum pyramidale interneurons). The specific layers in which these structures were found are known to receive intense excitatory input from the perforant pathway. High concentrations of reactive mitochondria were also observed within the somata and proximal dendrites of CA3 pyramidal cells and various interneurons, confirming our light-microscopic observations. These results demonstrated that not only can soma and dendrites of the same cell have disparate but distinct levels of cytochrome oxidase activity, but the pattern of reactivity within a neuron's apical and basal dendrites, or even within specific dendritic segments of the same dendrite can be quite different. While the levels of somatic reactivity correlate with reported levels of spontaneous and/or synaptic activity, the degree of dendritic and somatic staining appeared to be more closely related to the intensity of convergent and/or pathway-specific excitatory synaptic input.