Hot-foot mutant mice are characterized by defective arborization of Purkinje cell dendrites, resulting in ataxia of gait and deficits of equilibrium. Regional brain variations of cytochrome oxidase (CO) activity were analysed for the purpose of identifying those brain regions with abnormal metabolic activity as a secondary consequence to the cerebellar alteration. In addition, the possible relation between CO activity and motor deficits was evaluated. By comparison to normal littermate controls of the same background strain, hot-foot mutants had higher CO activity in the molecular layer of the cerebellum, the ventrolateral and midline thalamic nuclei, as well as in the frontal eye field. There was no other alteration of CO activity in the hot-foot brain. No linear correlation was discerned between CO activity in the molecular layer of the cerebellum and the ventrolateral and midline nuclei on one hand, and motor coordination performance on the other. These results indicate regionally selective abnormalities of metabolic activity in a cerebellar mutant with defective dendritic arborization of the Purkinje cell.