When the parotid glands of normal male and female ICR mice (12 weeks of age) were examined under a light microscope, no granular cells were seen in the duct system. However, transmission electron microscopy revealed that, in both sexes, many striated duct cells contained a few electron-dense secretory granules in their subluminal cytoplasm and had formed so-called granular striated tubules (GSTs) in some of the striated duct segments. These secretory granules were not large enough to be visible with a light microscope. Fully fledged granular cells, containing large secretory granules visible with a light microscope, could be induced in the GST segments of the glands of males by injection with 5alpha-dihydrotestosterone (DHT), triiodothyronine (T(3)), and dexamethasone (Dex), given alone or in combination every other day for 2 weeks. Dex alone showed no effect on the GSTs in this study. Both DHT and T(3), either individually or with Dex, were moderately effective, inducing a few scattered fully fledged granular cells. A stronger effect was detected after concomitant injection of DHT and T(3), with or without Dex, with more abundant fully developed granular cells appearing in the GST segments. Electron microscopy revealed that these granular cells had abundant large secretory granules in their apical two-thirds, a basal nucleus, and modest basal infoldings. By contrast, the effect of the same hormones was very weak in the glands of females, and even the concomitant injection of DHT and T(3), with or without Dex, rarely induced fully fledged granular cells. These results indicate a close similarity between the ductal systems of the major salivary glands of the mouse, in terms of some of the striated duct segments containing secretory granules, being under the same multihormonal regulation, and being sexually dimorphic.