Bartter syndrome represents a group of hereditary salt- and water-loosing renal tubulopathies caused by loss-of-function mutations in proteins mediating or regulating salt transport in the thick ascending limb (TAL). Mutations in the ROMK channel cause type II antenatal Bartter syndrome that presents with maternal polyhydramnios and postnatal life-threatening volume depletion. We have developed a colony of Romk-null mice showing a Bartter-like phenotype and with increased survival to adulthood suggesting the activation of compensatory mechanisms. To test the hypothesis that up-regulation of Na+- transporting proteins in segments distal to the TAL contribute to compensation, we studied expression of salt transporting proteins in ROMK-deficient (Romk-/-) mice. Plasma aldosterone was 40% higher and urinary PGE2 excretion was 1.5-fold higher in Romk-/- compared to wild-type littermates. Semi-quantitative immunoblotting of kidney homogenates revealed decreased abundances of proximal tubule Na+/H+-exchanger (NHE3) and Na+/Pi-cotransporter (NaPi-IIa) and TAL-specific Na+-K+-2Cl--cotransporter (NKCC2/BSC1) in Romk-/- mice, while the distal convoluted tubule (DCT)-specific Na+/Cl-- cotransporter (NCC/TSC) was markedly increased. The abundance of the ,,-subunits of the epithelial Na+-channel (ENaC) was slightly increased, though only differences for ENaC reached statistical significance. Morphometry revealed a 4-fold increase in the fractional volume of (DCT) but not of connecting tubule (CNT) and collecting duct (CCD). Consistently, CNT and CD of Romk-/- mice revealed no apparent increase in the luminal abundance of the epithelial sodium channel (ENaC) when compared with those of wildtype mice. These adaptive changes in Romk-/- mice may help to limit renal Na+ loss, and thereby, contribute to survival of these mice.