This histochemical study comprises a comprehensive overview of acid phosphatase distribution along the entire length of the digestive tract from esophagus through large intestine of growing and metamorphosing larvae and mature frogs of a single anuran species, Rana pipiens. The main site of enzyme localization throughout the length of the tube is the supranuclear area of the mucosal epithelium. However, activity of the enzyme varies markedly, not only in different locations (e.g., weak in the esophagus, strong in the small intestine), but also in different stages of larval development. During limb bud—early metamorphic stages (I—XX), activity is localized only in epithelial cells (supranuclear zone and scattered basal foci) and in glands of the stomach. Activity in these sites increases when remodeling of the digestive tract begins in the latter stages of this period. By mid-metamorphosis (XXI—XXII), shortening of the tract has become maximal, and acid phosphatase-positive epithelial cells have degenerated and sloughed into the lumen. In contrast, enzyme activity appears (albeit transitorily) in a new location, namely, in connective tissue thickening along the length of the tract. A similar histochemical picture can be induced precociously by thyroxine treatment. By the end of metamorphosis (XXIII—XXV), activity again appears in mucosal epithelium, but in newly differentiated adult-type cells as well as in gastric and initially-forming esophageal glands (the only two types of multicellular glands in the digestive tract). In adult frogs, activity remains in these sites and in scattered points (probably phagocytes) in the connective tissue; however, activity is generally weaker than in early-stage larvae.