According to some current hypotheses, the morphology and organization of the intercalated duct/acinar interface of salivary gland have implications for the induction of tumors in this organ. However, this region has received limited detailed investigation. To study the organization of the terminal ductal segments of salivary gland, conventional transmission electron microscopy of human parotid and submandibular glands and canine submandibular gland was combined with 3-dimensional observations of polymer casts of the canine submandibular ductal system; the latter were prepared by retrograde injection of acrylic resin via the main excretory duct with subsequent digestion of the gland tissue. The division of intercalated ducts, into first- and second-order branches, and acinar arrangement is more complex than previously suggested. The entire surface of each elongated second-order intercalated duct is covered with acini projecting in all directions. In the human gland, some acini abut directly on the intercalated duct surface, whereas others are connected by a short stalk of intercalated duct cells; in comparison with canine submandibular gland, the latter may be a modification producing a third-order of the intercalated duct unit. All of these features combine to produce a highly efficient secretory apparatus with a large proportion of acinar cells to each intercalated duct.