The structure of the rat parotid gland was studied in male rats from 4 hours up to 1 year after induction of diabetes by the administration of streptozotocin (STZ, 65 mg/kg). Blood glucose and triglyceride levels were markedly increased, and plasma insulin levels were significantly decreased within 24 hours after STZ. The earliest detectable alteration in acinar cell structure was the presence of small lipid droplets in the basal cytoplasm at 24 hours. Lipid accumulation continued, reaching a peak at 4.5 months after STZ, when the acinar cells contained large lipid vacuoles. By 1 week the Golgi apparatus was enlarged and GERL was prominent at the trans Golgi face. Membrane-bound cytoplasmic crystalloids occurred in acinar cells 1 month after STZ administration and were numerous in older animals (10 to 12 months). These crystalloids occasionally were reactive for trimetaphosphatase, a cytochemical marker for lysosomes. Similar crystalloids as well as large, dense, phagosome-like bodies were also present in the striated duct cells. Macrophages containing acinar cell debris and crystalloids were frequently observed, often in association with the intercalated ducts. Focal alterations in the basement membranes, consisting of multiple layers, loops, and amorphous patches, and "redundant" folds, occurred as early as 2 months and were relatively frequent 10 to 12 months after STZ administration. These results suggest that maintenance of the normal structure and function of the rat parotid gland may, in part, be insulin dependent.