In the multilayered epithelial membranes, topological factors, in addition to factors operating in cell units, must be considered in the regulation of ion transport. One such factor, i.e., the role of cell-to-cell junctions as regulators, is considered in the present computer simulation study. The primary aim was to correlate electron microprobe data on cellular Na+ pool sizes of frog skin with well-known rates of transepidermal Na+ influx and efflux under several laboratory conditions, including single or combined application of ouabain and amiloride. A complete kinetic analysis of data obtained on a simplified multicompartmental model of the epidermis suggests, on purely topological grounds, the occurrence in the epidermis of multiple physiological steady states in which Na+ is pumped transepidermally at equal rates but associated with very different states of intercellular Na+ flow dynamics. The possible significance of these multiple states for the understanding of the responses of the epidermis to perturbing influences is discussed.