Cell-surface proteins are believed to have important roles in cell-cell interactions during brain development, particularly in such processes as cellular adhesion, neurite outgrowth and synapse formation. The chick neural cell adhesion molecule, CAM, is a cell-surface protein specific to the nervous system and has been implicated in cell adhesion among cells and neurites of the developing retina and brain. Previous studies have shown that F(ab') fragments of antibodies directed against CAM inhibit the in vitro aggregation of cells obtained from 9-day embryonic chick retina. The specific antibody fragments also reduce the diameter of neurite fascicles that grow out from cultured dorsal root ganglia, apparently by blocking side-to-side adhesion between the neurites. In addition, anti-CAM antibodies alter the appearance of histotypic patterns in retinal cell aggregates maintained in culture for several days. We now demonstrate that the antibodies can disrupt histogenesis of the developing retina in organ culture, strengthening the notion that the cell-cell adhesion properties mediated by CAM are involved in the normal development of histological layers in the chick retina.