THE amiloride-sensitive epithelial sodium channel constitutes the rate-limiting step for sodium reabsorption in epithelial cells that line the distal part of the renal tubule, the distal colon, the duct of several exocrine glands, and the lung. The activity of this channel is upregulated by vasopressin and aldosterone, hormones involved in the maintenance of sodium balance, blood volume and blood pressure^1,2. We have identified the primary structure of the α-subunit of the rat epithelial sodium channel by expression cloning in Xenopus laevis oocytes³. An identical subunit has recently been reported⁴. Here we identify two other subunits (β and γ) by functional complementation of the α-subunit of the rat epithelial Na⁺ channel. The ion-selective permeability, the gating properties and the pharmacological profile of the channel formed by coexpressing the three subunits in oocytes are similar to that of the native channel.