The plant polyphenol quercetin was shown to induce a significant CI- secretion in intestinal epithelium. In order to elucidate the structural requirements of quercetin and related flavonoids for this activity, we tested the ability of further flavonols and other flavonoids found in edible plants to induce CI- secretion which was measured as an increase in short-circuit current (I(SC)) in rat colon. Whereas several flavonols and the flavon luteolin increased I(SC), other flavonoids such as flavanones, flavans, flavanols, and anthocyanidins failed to do so. Two glycosides of quercetin, spiraeosid, and isoquercitrin, as well as two methoxylated quercetin metabolites, isorhamnetin and tamarixetin, were also able to increase I(SC). We conclude that a 2,3-double bond in conjunction with the 4-oxo group in the C ring and a hydroxylated B ring are necessary for the secretory activity of flavonoids. This activity requires different structural features than those mandatory for the antioxidative properties of flavonoids. Glucosidation and methoxylation of several hydroxyl groups does not necessarily abolish the secretory potential.