The neuronal growth cone is a highly motile and adhesive structure, leading to maintain and promote neurite outgrowth. Using immunocytochemical and biochemical techniques, we investigated the regional distribution of the membrane cytoskeletal proteins, such as α-actinin, calspectin (nonerythroid spectrin or fodrin) and actin, and the proto-oncogene product, pp60c-src, in the growth cone. During a course of this study, the two types of α-actinin, having Ca2+-sensitive and -insensitive actin-binding abilities, were identified. These three membrane cytoskeletal proteins and pp60c-src showed discrete differential distributions coinciding with the different functions of the growth cone substractures. Ca2+-sensitive α-actinin, calspectin and pp60c-src were observed to localize in the growth cone body and the distal portion of neurites, which are the adhesive sites of growth cone and neurite. By contrast, Ca2+-sensitive α-actinin and actin were densely concentrated in the filopodia, These results suggest that Ca2-insensitive α-actinin, calspectin and pp60c-src may be involved in adhesiveness of growth cone, and Ca2+-sensitive α-actinin and actin in Ca2+-dependent filopodial movement. Furthermore, we will discuss the functional and structural similarities between the growth cone and the motile contact which is also the adhesive site of motile, transformed and cancer cells. © 1990.