Summary: Monoclonal antibody 303 (mAb 303) reacts with the high molecular weight agglutinin present in human saliva. Its reactivity is periodate sensitive, and it has been shown to recognize the Y epitope. Immunogold labeling of thin sections of human parotid and submandibular glands with mAb 303 showed reactivity in secretory granules of serous acinar, intercalated and striated duct cells (Takano et al., 1988). We now report that the apical and basolateral membranes of salivary acinar and duct cells are labeled by mAb 303, but not myoepithelial cells, endothelial cells and other mesenchymal cells. Gold particles were confined to acinar and duct cell membranes even when myoepithelial cells were directly adjacent, suggesting that the epitope resides on a membrane glycoprotein and that the label does not represent secreted agglutinin bound to the cell surface. Although myoepithelial cells are thought to differentiate from epithelial stem cells, the present results indicate that substantial compositional differences exist between the membranes of myoepithelial cells and other salivary parenchymal cells. Earlier studies also showed that mAb 303 labels normal pancreatic acinar cells and certain salivary (pleomorphic adenoma) and mammary (lactating adenoma) tumors (Bogert et al., 1988). This antibody thus may be a useful reagent for characterizing the origin of exocrine gland-derived cell cultures and neoplastic cells. Further, localization studies may provide insight into the role of the Lewis blood group-related epitope in secretory cells.The origin of myoepithelial cells (MECs) in the normal salivary glands is still under investigation. MECs are a prominent component of a number of neoplasms of developing epithelial cells. Therefore, MECs are thought to differentiate from epithelial stem cells. However, MECs resemble smooth muscle cells by electron microscopy and cytochemistry, and also are considered to have a contractile function. In developing hamster submandibular gland, four cell types can be recognized by electron microscopy in the terminal tubule at 131/2 days of gestation (Chaudhry et al., 1983). One of these cell types represents the initial identifiable myoepithelial cell precursors. The cells of this type are distributed between the basal lamina and other cells of the terminal tubules. However, cytoplasmic filaments, which are the dominant characteristic of the myoepithelium could not be seen in their cytoplasm. Therefore, MECs are difficult to distinguish ultrastructurally from other epithelial stem cells during the early stages of gland differentiation. In early studies, MECs were identified by histochemical reactions, such as reactions for alkaline phosphatase (Dempsey et al., 1947, Leeson, 1956, Bogart, 1968, Garrett and Harrison, 1970, for adenosine triphosphatase (Shear, 1964, Nagashima andOno, 1985), or for TP-LFC Ball, 1979, Redman et al., 1980), and also identified by early immunohistochemical studies (Archer and Kao, 1968, Line and Archer, 1972, Drenckhahn et a!., 1977. However, the results o...