Using electrophysiological techniques, the apical membrane ionic permeabilities of primary cell cultures of the mouse mammary gland in the midpregnant, preneoplastic and neoplastic states were examined. Membrane Na+ permeability changed with tumorigenesis, whereas K+ and Cl- permeabilities were unaltered. With tracer flux techniques the unidirectional efflux rate constant of 22Na was greater in tumor cells than in normal cells. This increase in 22Na efflux was eliminated by the addition of ouabain. The results are interpreted as an increase in Na+ permeability and in Na+-K+-ATPase activity with neoplastic transformation. The presence or absence of the virus in midpregnant cells does not seem to affect Na+ permeability.