Defective colonic Na⁺ and Cl^- absorption is a feature of active ulcerative colitis (UC), but little is known about changes in colonic K⁺ transport. We therefore investigated colonic K⁺ transport in a rat model of dextran sulfate-induced colitis. Colitis was induced in rat distal colon using 5% dextran sulfate sodium (DSS). Short-circuit current (Isc, indicating electrogenic ion transport) and ⁸⁶Rb (K⁺ surrogate) fluxes were measured in colonic mucosa mounted in Ussing chambers under voltage clamp conditions in the presence of mucosal orthovanadate (a P-type ATPase inhibitor). Serum aldosterone was measured by immunoassay. Control animals exhibited zero net K⁺ flux. By contrast, DSS-treated animals exhibited active K⁺ secretion, which was inhibited by 98%, 76% and 22% by Ba²⁺ (nonspecific K⁺ channel blocker), iberiotoxin (IbTX; BK channel blocker) and TRAM-34 (IK channel blocker), respectively. Apical BK channel α-subunit mRNA abundance and protein expression, and serum aldosterone levels in DSS-treated animals, were enhanced 6-, 3- and 6-fold respectively, compared with controls. Increasing intracellular Ca²⁺ with carbachol (CCH), or intracellular cAMP with forskolin (FSK), stimulated both active Cl^- secretion and active K⁺ secretion in controls, but had no or little effect in DSS-treated animals. In DSS-induced colitis, active K⁺ secretion involves up-regulation of apical BK channel expression which may be aldosterone-dependent, whereas Cl^- secretion is diminished. Since similar ion transport abnormalities occur in patients with UC, diarrhoea in this disease may reflect increased colonic K⁺ secretion (rather than increased Cl^- secretion), as well as defective Na⁺ and Cl^- absorption.