Two cases of diabetes mellitus in juvenile dogs (a 3-4 month-old Golden Retriever and a 2-month-old Labrador Retriever) are described here in terms of their clinical, histologic, and immunohistologic findings. Only very few insulin-positive cells were demonstrated immunohistochemically in one dog. In the second dog, the alterations of the pancreas consisted of hydropic vacuolar degeneration of B cells in the islets of Langerhans. In both cases, hyperplasia of the vacuolated cells was prominent. These cells formed tubular structures and were immunohistochemically positive for cytokeratin and proliferating cell antigen (MIB-1). Furthermore, within these vacuolated areas, some cells were positive to varying degrees for insulin, glucagon, somatostatin, and pancreatic polypeptide. Apoptotic cells could be seen in the exocrine pancreas, in vacuolated areas, and occasionally in the islets of both dogs. We interpret these alterations as ductuloendocrine cell proliferation, probably as an idiopathic compensatory response.