The active absorption of water from the surface of epithelial cells in the gas exchanging region of the lungs is dependent upon electrogenic Na⁺ transport via epithelial sodium channels (ENaC). Regulation of ENaC expression involves the activity of serum and glucocorticoid-dependent kinase-1 (SGK1). Previous evidence suggests that the protein kinase mammalian target of rapamycin (mTOR) may control Na⁺ coupled solute transport via an intracellular signalling pathway shared with SGK1 (Shojaieford and Lang, 2006; Shojaieford et al., 2006). The aim of this study was to examine if over expression of a constitutively active mTOR activating protein, Ras homologous enriched in brain (Rheb), induced sodium channel expression in a manner analogous to over expression of SGK1 in single human lung H441 epithelial cells using perforated patch clamp electrophysiology. Sodium conductance (G_Na, NMDG⁺ substitution) is negligible in cells cultured in hormonally deprived conditions (0.03±0.020 nS cell^-1). In hormonally deprived, Rheb expressing cells NMDG⁺ substitution revealed a [Na⁺]_o dependent depolarisation of V_m (control: -16.2±2.0mV; low Na⁺ -52.4±3.3mV, P<0.001). The Rheb induced Na⁺ conductance is rapamycin sensitive (rheb: 1.80±0.7 nS cell^-1; Rheb + rapamycin 0.51±0.07 nS cell^-1, P<0.01, n=10). Surprisingly, overexpression of Rheb (D60V), a mutant form that does not bind guanine nucleotides, also induced a sodium conductance (0.21±0.1 nS cell^-1, n=5). Similar to previous findings (Shojaieford et al., 2006), expression of a catalytically inactive form of SGK1 (K127A) significantly reduced the Rheb induced sodium conductance (Rheb: 1.91±0.41 nS cell^-1, Rheb + SGK1-K127A 0.41±0.08 nS cell^-1, P<0.001, n=5). Like the SGK1 induced Na⁺ conductance (Brown et al., 2008), the Rheb induced Na⁺ conductance in single H441 cells is amiloride insensitive. Thus mTOR and SGK1 may increase G_Na through a shared mechanism.