Cultured cells from either chicken lens or liver plated on solid substrates form flat epithelial sheets with adherens-type junctions between them. In lens cells these junctions contain A-CAM, while the same type of intercellular junctions in liver cells contain another cell adhesion molecule, L-CAM. Coculturing of lens and liver cells in the same dish resulted in the formation of mixed (heterotypic) adherens junctions. Double immunofluorescent labeling for both A-CAM and L-CAM indicated that the mixed junctions contained both molecules, each of which was present on one of the two partner cells. Moreover, the formation of the heterotypic junctions could be effectively inhibited by both anti-A-CAM and anti-L-CAM antibodies. It has thus been proposed that A-CAM and L-CAM share significant functional homology and may be involved in heterophilic interactions leading to the establishment of molecularly and cellularly asymmetrical adherens-type junctions.