Abstract Whole skins and isolated epithelia were bathed with isotonic media (- 244 mOsm) containing sucrose or glucose. The serosal osmolality was intermittently reduced (to - 137 mOsm) by removing the nonelectrolyte. Transepithelial and intracellular electrophysiological parameters were monitored while serosal osmolality was changed. Serosal hypotonicity increased the short-circuit current (I sc) and the basolateral conductance, hyperpolarized the apical membrane ( Φ mc), and increased the intracellular Na + concentration. The increases in apical conductance and apical Na + permeability (measured from Goldman fits of the relationship between amiloride-sensitive current and Φ mc) were not statistically significant. To verify that the osmotically induced changes in I sc were mediated primarily at the basolateral membrane, the basolateral membrane potential of the experimental area was clamped close to 0 mV by replacing the serosal Na + with K + in Cl −-free media. The adjoining control area was exposed to serosal Na +. Serosal hypotonicity produced a sustained stimulation of I sc across the control, but not across the adjoining depolarized tissue area. The current results support the concept that hypotonic cell swelling increases Na + transport across frog skin epithelium by increasing the basolateral K + permeability, hyperpolarizing the apical membrane, and increasing the electrical driving force for apical Na + entry.