To test the hypothesis that colonic Na⁺ transport is altered in the 5/6 nephrectomized rat model of chronic renal failure (CRF), we measured Na⁺ fluxes across distal colon from control (CON), CRF, and CRF rats treated with the angiotensin II (ANG II) receptor antagonist losartan (+ LOS). We also evaluated overall fluid and Na⁺ balance and compared colonic protein and mRNA expression profiles for electroneutral (NHE) and electrogenic Na⁺ transport (ENaC) in these groups. Consistent with a 60% enhancement in colonic Na⁺ absorption in CRF, urinary Na⁺ excretion increased by about 50% while serum Na⁺ homeostasis was maintained. These CRF-induced changes in Na⁺ handling were normalized by treatment with LOS. Net Na⁺ absorption was also stimulated in in vitro tissues from CON rats following acute serosal addition of ANG II (10^-7 M) and this increase was blocked by AT₁ antagonism, but not by an AT₂ antagonist. In CRF, colonic protein and mRNA expression variably increased for apical NHE2, NHE3, and ENaC -, -, -sub-units, while expression of basolateral NHE1 and Na⁺-K⁺-ATPase (-isoform) remained unaltered. Upregulation of the ENaC subunit mRNA was attenuated somewhat by LOS treatment. Previously, we showed that colonic AT₁ receptor protein is upregulated 2-fold in CRF and here we find AT₁ and AT₂ mRNA and AT₂ protein abundance is unchanged in CRF. We conclude that Na⁺ absorption in CRF rat distal colon is increased due to elevated expression of proteins mediating electroneutral and electrogenic uptake and that it is partially mediated by AT₁ receptors.