The role of angiotensin II (ANG II) in colonic secretion of K⁺ was examined in rats with chronic renal failure (CRF). The basal net secretory flux of ⁸⁶Rb⁺ (as a tracer for K⁺) across the CRF distal colon (0.20 ± 0.04 µeq · cm² · h¹) was reversed to an absorptive flux (0.35 ± 0.05 µeq · cm² · h¹) by injecting the rats with the AT₁ receptor antagonist, losartan. A similar result was observed when losartan was added to the CRF colonic tissue in vitro. In contrast, an AT₂ receptor antagonist, PD-123319, did not reverse the CRF-induced alterations in Rb⁺ transport across the short-circuited colonic tissue. Plasma concentrations of ANG II, aldosterone, and K⁺, as well as the ANG II content of colonic tissues from CRF and normal rats, were similar. However, specific ¹²⁵I-labeled ANG II binding sites in rat distal colon increased twofold in CRF [maximal specific binding (B_max) = 28.6 ± 1.6 fmol/mg protein] compared with normal (B_max = 15.2 ± 0.4 fmol/mg protein). These studies suggest that CRF-induced secretion of K⁺ by the colon is mediated by an upregulation of AT₁ receptors present in CRF.