Formation of gastric mucosal lesions by streptozotocin-induced diabetes was investigated in rats. A single intravenous administration of streptozotocin in a dose of 65 mg/kg effectively produced hyperglycemia and damaged the gastric mucosa. Incidence and severity of mucosal lesions were progressively increased with time, from one to six weeks posttreatment. Microscopic lesions of the mucosa included hyperemia, desquamation of the surface epithelium with diffuse hemorrhage, and severe hemorrhage with localized erosion. Concurrent to the hyperglycemia, the histamine stimulated gastric H+-secretion was significantly decreased whereas pepsin secretion was not affected. Both soluble mucus and surface mucus gel were increased. The result suggests that the early lesion of gastric mucosa may be associated with the direct action of streptozotocin, the severity of which may be further aggravated by diabetic state.