Fibronectin was localized in fetal and adult human skin with affinity-purified antibodies, using a ferritin staining technique. The most common observation was a close association of this fibronectin with thin and thick cross-striated fibrils containing collagens types I and III. Deposits of fibronectin occurred in discrete spots, with some regular distribution, in agreement with a major binding site for this protein on collagen. Fibronectin was also detectable at the periphery of elastic fibrils and in amorphous, non-fibrillar regions of skin. The latter pattern included a close pericellular localization, indicating interactions between fibronectin and plasma membranes. Discrete deposits of fibronectin were also found on the lamina lucida of the basement membrane of the dermal-epidermal junction and around small blood vessels. This widespread distribution of fibronectin suggests that it has a multitude of biologic functions in situ.