Corticosteroid control of distal nephron sodium handling, particularly through the amiloride-sensitive sodium channel (ENaC), has a key role in blood pressure regulation. The mechanisms regulating ENaC activity remain unclear. Despite the generation of useful mouse models of disorders of electrolyte balance and blood pressure, there has been little study of distal nephron sodium handling in this species. To investigate how corticosteroids regulate ENaC activity we isolated cDNA for the three mouse ENaC subunits (alpha, beta and gamma), enabling their quantitation by competitive PCR and in situ hybridisation. Kidneys were analysed from mice 6 days after adrenalectomy or placement of osmotic mini-pumps delivering aldosterone (50 microg/kg per day), dexamethasone (100 microg/kg per day), spironolactone (20 mg/kg per day) or vehicle alone (controls). In controls, renal ENaCalpha mRNA exceeded beta or gamma by approximately 1.75- to 2.8-fold. All subunit mRNAs were expressed in renal cortex and outer medulla, where the pattern of expression was fully consistent with localisation in collecting duct, whereas the distribution in cortex suggested expression extended beyond the collecting duct into adjacent distal tubule. Subunit mRNA expression decreased from cortex to outer medulla, with a gradual reduction in beta and gamma, and ENaCalpha decreased sharply ( approximately 50%) across the outer medulla. Expression of ENaCbeta and gamma (but not alpha) extended into inner medulla, suggesting the potential for inner medulla collecting duct cation channels in which at least ENaCbetagamma participate. Aldosterone significantly increased ENaC subunit expression; the other treatments had little effect. Aldosterone caused a 1.9- to 3.5-fold increase in ENaCalpha (particularly marked in outer medullary collecting duct), but changes for beta and gamma were minor and limited to the cortex. The results raise the possibility that medullary ENaCalpha upregulation by aldosterone will create more favourable subunit stoichiometry leading to a more substantial increase in ENaC activity. In cortex, such a mechanism is unlikely to have a major role.