The immunohistochemical distribution of keratin is reported in experimental carcinogenesis in the mouse submandibular gland (SMG). The initial changes included degranulation of granular convoluted tubule (GCT) cells and the appearance of keratin in the degranulated cells. There was a gradual increase in the area showing keratin staining in the altered tubule cells. Duct-like and cystic structures exhibited an intense keratin staining of their lining epithelium. The squamous cell carcinomas induced varying degrees of keratinization and positive immunohistochemical keratin staining. The latter technique provided a useful marker for distinguishing tumor cells of segmental duct origin in the salivary gland.