The distribution of amyloid beta precursor protein (APP) in canine brain was investigated. By immunoblot analysis, APP-positive bands corresponding to proteins of 105-120 kilodalton were recognized in all canine brains regardless of the individual age of the dogs. Bands of similar molecular mass were also detected in the meninges, cerebrospinal fluid, and several visceral organs. Immunohistochemical studies were performed using cryostat and paraffin-embedded sections pretreated with formic acid or by the hydrated autoclave method. In the normal canine brain, APP was found to be distributed in the neurons and vascular system. In the brains with SP, obvious accumulation of APP was observed in swollen neurites within amyloid plaques, although the relationship between APP and diffuse plaques was unclear. APP accumulation in swollen axons was also seen around necrotic foci in the brain of one dog with necrotizing purulent encephalitis. These studies revealed that distribution of APP in canine tissues, especially in the brain, and the accumulation of APP in swollen neurites or axons.