The aim of this study was to investigate the possible effects of the flavonol quercetin, the most abundant dietary flavonoid, on the intestinal mucosa. In vitro experiments were performed with various segments of the rat intestine, using the Ussing chamber technique. Quercetin increased the short-circuit current (I_sc) in the jejunum, ileum, and proximal and distal colon. Additional experiments were performed using preparations of the proximal colon. The maximum effective dose of quercetin was found to be ~100 µM. The quercetin-induced increase in I_sc was inhibited by the Cl channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoic acid. Adding blockers of the Na⁺-K⁺-2Cl cotransporter to the serosal compartment diminished the increase of I_sc due to quercetin. Ion substitution and flux measurements indicated that the effect of quercetin was due to electrogenic Cl and HCO₃ secretion. In contrast to the aglycone, the quercetin glycoside rutin had no effect. The effect of quercetin on I_sc was additive to the I_sc increase induced by forskolin, but the flavonoid diminished the I_sc evoked by carbachol. The phosphodiesterase inhibitor theophylline blocked the effect of quercetin. Genistein, a related isoflavone, did not alter the I_sc evoked by quercetin. These findings demonstrate that the dietary flavonol quercetin induces Cl secretion and most likely HCO₃ secretion in rat small and large intestine. The effects are restricted to the flavonol aglycone.