Extracellular matrix molecules such as laminin, fibronectin and collagen promote neurite outgrowth in vitro. We have investigated the capacity of hydrated gels of collagen types I-III and monomeric collagen types I-VI on plastic surfaces to support neuritogenesis. The attachment and survival of explants from the day 6 chick embryo were studied and neurite outgrowth measured as mean elongation rate and maximal neurite length. Collagen types I and III, both as three-dimensional gels or as native monomers supported neuritogenesis equal to or better than laminin. Collagen type V also supported neurite out-growth although less effectively. Collagen types II, IV and VI, as well as denatured collagens of all types tested, did not support outgrowth. The monoclonal anti-beta 1 integrin antibody (CSAT), as well as rabbit polyclonal antibodies directed to the integrin beta 1-chain, effectively inhibited neurite outgrowth on permissive collagenous substrata, indicating that collagen-binding integrins were involved in the neuritogenesis. These beta 1-integrins were independent of Arg-Gly-Asp (RGD) since neurite formation proceeded in the presence of synthetic RGD-containing peptides. Fluorescence immunohistochemistry revealed the presence of the integrin beta 1-chain on the outgrowing neurites. The results suggest a possible function of collagen and collagen-binding integrins in the development of the visual system.