Analysis of membrane currents recorded from hormone-deprived H441 cells showed that the membrane potential (V_m) in single cells (~ 80 mV) was unaffected by lowering [Na⁺]_o or [Cl^-]_o indicating that cellular Na⁺ and Cl^- conductances (G_Na and G_Cl respectively) are both negligible. Although insulin (20 nM, ~24 h) and dexamethasone (0.2 µM, ~24 h) both depolarized V_m by ~20 mV, the response to insulin reflected a rise in G_Cl mediated via 3-phosphatidylinositol phosphate kinase (PI3K) whilst dexamethasone acted by inducing a serum and glucocorticoid-regulated kinase 1- (SGK1) dependent rise in G_Na. Whilst insulin stimulation / PI3K-P110 expression did not directly increase G_Na, these manoeuvres augmented the dexamethasone-induced conductance. The glucocorticoid / SGK1 induced G_Na in single cells discriminated poorly between Na⁺ and K⁺ (P_Na / P_K ~0.6), was insensitive to amiloride (1 mM) but was partially blocked by La³⁺ (1 mM, ~80%), pimozide (0.1 mM, ~40%) and dichlorobenzamil (15 µM, ~15%). Cells growing as small groups, on the other hand, expressed an amiloride-sensitive (10 µM), selective Na⁺ conductance that displayed the same pattern of hormonal regulation as the non-selective conductance in single cells. These data (i) confirm that H441 cells can express selective or non selective Na⁺ conductances (M.T. Clunes et al. J. Physiol. 557: 809-819, 2004; V. Shlyonsky et al. J. Biol. Chem. 280: 24181-24187, 2005); (ii) show that these conductances are both induced by glucocorticoids / SGK1 and subject to PI3K-dependent regulation; and (iii) establish that cell-cell contact is vitally important to the development of Na⁺-selectivity and amiloride-sensitivity.