Canine Inherited Ataxia is inherited as an autosomal recessive trait in Gordon Setters. This animal model shares features with certain human cerebellar degenerations and offers the opportunity to examine brain tissue at various stages during the evolution of disease. The present investigation focuses on the morphometric and ultrastructural changes of cerebellar neurons. Purkinje and granule cells are the principal intrinsic neurons at risk. The size of Purkinje cells decreases, axonal degeneration is an important feature of the pathology, and synaptic abnormalities occur in the cerebellar glomeruli and deep nuclei of the cerebellum. The sequence and nature of synaptic changes in the molecular layer suggest that the degenerative process begins in Purkinje cells and that granule cells may be secondarily affected.