Four cases of spontaneous adenocarcinoma of the canine exocrine pancreas were studied by thin section and freeze-fracture electron microscopy. The neoplastic cells in all 4 cases were of acinar origin and showed many alterations of cytoarchitecture compared with normal acinar cells. In the neoplastic cells, zymogen granules varied in number and appearance and contained an abnormal secretory product characterized by 24-nm-thick microtubules. The nuclear volume and surface area and the nuclear cytoplasmic ratio were increased; although the nuclear pore density per nuclear surface area was significantly decreased, there was no change in the nuclear pore density per nuclear volume. There was a decrease in number and size of gap junctions; focal proliferation, fragmentation, and discontinuation of the tight junctions were also noted. The basal lamina (BL) of the neoplastic cells was discontinuous. The tumor microvasculature often appeared as sinusoids and had sparse discontinuous BL. Finally, the endothelium in both tumor and normal tissue contained "tubulo-reticular inclusions" (TRI) which simulated distemper virus and were located in the rough endoplasmic reticulum (RER) and the perinuclear cisternae.