AbstractThe pathology of canine glycogen storage disease type II (acid α‐glucosidase deficiency, GSD II) was studied in three genetically related Lapland dogs and compared to the pathology of human GSD II (McKusick 23230). Canine GSD II closely parallels the infantile form of the human disease, except for the presence of oesophageal dilatation. Generalized glycogen storage particularly affected muscular tissues (skeletal, oesophageal, cardiac and smooth muscle). The altered cells showed glycogen accumulation in the cytosol and in autophagic membrane‐bound vacuoles (glycogenosomes). They also showed increased acid phosphatase activity consistent with the lysosomal nature of this storage disorder. The cytopathology in canine and human GSD II appears to evolve from segregation of glycogen during regular cellular autophagy, phagolysosomal accumulation of the undigested glycogen, and eventually rupture of distended glycogenosomes. This study indicates that the usefulness of canine GSD II as an animal model of human disease, extends to the area of pathogenesis.