This study describes the immunocytochemical localization of fibronectin, a defined connective tissue and plasma glycoprotein, and its relationship to collagen and reticulin in adult newt limb tissues. We have also isolated the plasma form of fibronectin in a related species, the adult mudpuppy. The insoluble form of fibronectin was detected with immunoperoxidase stain in basement membranes and loose connective tissue. The endoneurium and perineurium of nerve bundles and the connective tissue elements of striated muscle stained heavily for fibronectin. The dermis and blood vessel walls also reacted positively with the immunoperoxidase stain. A similar distribution was observed for reticulin with conventional histologic techniques with the exception of the dermis where only trace amounts of the protein were observed. Fibronectin and collagen were codistributed in the tissues studied. Fibronectin appeared to be intercalated among larger collagenous fibers. Collagen and fibronectin form an extracellular connective tissue scaffold that abuts against many types of adherent cells in different tissues. This supports the possible role of fibronectin in cell-matrix interactions and normal cell and tissue organization.