MDCK cells in culture form a functional transporting epithelium. Apical surface of MDCK monolayers are not adhesive to free MDCK cells that fail to grow attached to existing monolayers. In contrast, when plated at high density (106 cm-2) MDCK cells form multilayered structures in which only the outermost layer shows a typical apical surface (microvilli, tight junctions, etc). In the lower layers cell-cell contacts (desmosomes, etc) are made, suggesting that the basolateral surfaces remain adhesive. Using a novel, quantitative, heterotypic cell adhesion reaction with aged human red cells, were have measured the adhesive properties of the apical surfaces of MDCK cells in a variety of conditions. It is found that the adhesion of red cells is dependent on cell density in the monolayer and falls to a low value at confluence. The reaction is considerably stronger at 6 degrees C compared to 22 degrees C (the temperature of most studies), while at 37 degrees C the reaction is expressed less strongly. MDCK cells with adherent red cells fail to divide, suggesting that the cell surface fluence. The expression of the adhesive property is associated with cell division. This was shown by inducing synchrony in cultures either by refeeding starved cultures or by removal of a thymidine " block". Peaks in adhesiveness were related to peaks in thymidine incorporation in synchronized cultures. Because of the precise quantitative way in which adhesion can be measured it is considered that this is an ideal system in which to identify the membrane components responsible for the reaction. Furthermore, it may prove possible to identify signals that arise as an immediate consequence of the adhesion reaction.