Lectin-binding and histochemical studies were integrated with a morphological description of colon development in rat fetuses to determine whether changes in glycoprotein sugars could be identified with stages of colon organogenesis. At 16 days gestation the colon consisted of a minute lumen surrounded by 3-5 layers of cuboidal, stratified epithelium, a basement membrane and undifferentiated mesenchyme. As development proceeded, epithelial spaces eventually fused with the main lumen, and fingers of mesenchyme, with a basement membrane and epithelial mantle, formed the walls of crypts lined with simple to stratified columnar cells. Goblet cells and mucin production appeared only on the 20th-21st day of gestation. Mesenchyme differentiation to a circular muscle band, the prospective tunica muscularis, occurred on days 17-18, and vascularization of the lamina propria was first detected on day 19. Wheat germ agglutinin (WGA) lectin bound avidly to sugar residues in the mesenchyme matrix from day 16 but weakened as the tissue differentiated, particularly into smooth muscle. Alcian blue staining of the matrix, also weakening with time, confirmed the sialic acid nature of binding sites for WGA on matrix acid mucopolysaccharides. Under controlled conditions, WGA also detected N-acetylglucosamine-binding sites on brush borders as they developed on the apical surface of primitive enterocytes. Ulex lectin bound to fucose residues of Alcian-blue-positive, PAS-positive mucin from the first appearance of goblet cells. Concanavalin A and glycine max lectins bound only to blood group substances on both nucleated red cells between days 16 and 19 and anucleate red cells from day 19.(ABSTRACT TRUNCATED AT 250 WORDS)