Epithelial cells, and the tight junctions between them, form a polarized barrier between luminal and serosal fluid compartments and segregate luminal growth factors from their basal-lateral receptors. Breakdown of this barrier should allow access of growth factors in the luminal fluid to their receptors on the basal-lateral cell membranes, as recently demonstrated for heregulin and erbB receptors in airway epithelia. It should also allow luminal growth factors to access the stroma. This property may have adaptive value for epithelial tissues in general, as an elegant response to injury, but may also promote cancer formation in premalignant epithelial tissues in which the tight junctions have become chronically leaky to growth factors.