AbstractThe beta‐amyloid precursor protein (APP) is a membrane‐bound glycoprotein which has been proposed to play a role both as a growth factor and a mediator of cell adhesion. Using the Ncuro‐2A neuroblastonia cell line, we have investigated the capacity of APP to mediate neural cell adhesion. The cells express the protein at a high level, the immunohistochemical staining pattern at the level of the membrane having a punctate pattern. Fab' fragments of antibodies to the extracellular portion of the molecule were found to inhibit cell binding to a collagen substrate, but not to laminin, fibronectin, or poly‐I‐lysine. Fab' fragments of antibodies to the nerve cell adhesion molecule N‐CAM also inhibited binding of Neuro‐2A cells specifically to collagen. This inhibition of cell‐surface binding was accompanied by a repression of neurite outgrowth in differentiating cells in the presence of antibodies. APP antibodies also inhibited neuron‐neuron and neuron‐glial binding, but not glial‐glial cell adhesion. These data suggest that the APP, which is expressed primarily on differentiated neuronal cells, may play a role in the mediation of both cell‐cell and