Background and Aims: The role of cell adhesion molecules in colonic organogenesis remains poorly understood. This study examined the expression of α-integrin subunits and extracellular matrix ligands during human colonic development. Methods: Standard immunohistochemistry was used to characterize extracellular matrix and α-integrin subunit expression during development. Results: At 9 weeks, type-IV collagen and laminin were present underlying epithelium, around vascular structures, and surrounding inner circular muscle layer fibers. Fibronectin was uniformly expressed in the mesenchyme. Tenascin distribution was restricted to the presumptive muscle layer and, later, to the villus core and muscularis mucosae. The 9-week epithelium expressed α2, α3, α5, and α8, and, by 11 weeks, α9, α3, α6, and α8 expression was accentuated at the basal membrane. During transition from pseudostratified to simple columnar epithelium, a vertical α2 gradient formed. Mesenchymal cells expressed α5 and α8 by 9 weeks. The developing muscularis (propria and mucosae) showed accentuated α5 expression. By 16 weeks, α8 expression localized to the muscularis mucosae and villus core. Mesenchymal vascular elements stained strongly with anti-α2 and α6 by 9 weeks. Conclusions: These observations show the complexity and overlap of adhesive receptor expression and ligands during development and reveal early cell commitment to the formation of specific structures.