Hsp110 is one of the few, major heat shock proteins of mammalian cells and was one of the earliest heat shock proteins described. However, it has only recently been cloned and studied at the molecular level. It has been noted that of all tissues examined, brain expresses the highest level of hsp110, with expression levels in unstressed brain being similar to the levels seen in heat shocked cells. The present report describes a combined Northern and Western blot analysis of hsp110 expression in various regions of mouse and human brain. These observations are further expanded by an immunohistochemical characterization of hsp110 cellular localization in mouse brain. It is seen that although hsp110 is an abundant protein in most regions of the brain, its expression is heterogeneous, with little being detectable in the cerebellum. Within the cerebral hemispheres, hsp110 is present in neurons in all regions including the cerebral cortex, the hippocampus, the thalamus and the hypothalamus. In contrast, in the cerebellum, the Purkinje cells are the major hsp110 containing cells while the more abundant granule cells show little if any hsp110 labeling. Since hsp110 has been shown to protect cells and proteins from thermal damage, this differential pattern of expression may have ramifications in the pathophysiology of brain, specifically involving cerebellar sequelae.