Early events of tumor promoting phorbol esters are changes in properties of cell membranes which are considered of crucial importance in the regulation of cell growth and differentiation. We have observed that the potent tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulates the plasma membrane (Na ion plus K ion)-ATPase, and it is of interest to learn whether this effect is mediated by intracellular Ca2 ion release (possibly from membrane-bound Ca2 ion), or changes in membrane potential, and whether this stimulatory effect is shared by retinoids, beta-receptor agonists, or intermediates of arachidonic acid metabolism. Therefore TPA-stimulated 86Rb ion uptake will be examined in the presence of agents which interfere with each of these processes, e.g. chloropromazine, beta-adrenergic antagonists, and inhibitors of lipoxgenase activity. Further, it will be of interest to see whether Ca2 ion efflux is promoted by TPA under conditions of preloading mouse fibroblasts with 45Ca2 ion, and to learn with the use of radioautography, changes in Ca2 ion distribution.