-OH-flavonoids disappeared more rapidly from human fecal incuba- tions and were less absorbable by humans than flavonoids without 5-OH moieties. Anaerobic fecal disappearance rates over 24 h were determined for 15 flavonoids in samples from 20 men and 13 women. In these anaerobic fecal mixtures, flavonoids with 5,7,40-OH groups, genistein, apigenin, naringenin, luteolin, kaempferol, and quercetin (disappearance rate, k = 0.46 ( 0.10 h-1), and methoxylated flavonoids, hesperetin and glycitein (k = 0.24 ( 0.21 h-1), disappeared rapidly compared with flavonoids lacking 5-OH (e.g., daidzein, k = 0.07 ( 0.03 h-1). Apparent absorption of flavonoids that disappeared rapidly from in vitro fecal incubations, genistein, naringenin, quercetin, and hesperetin, was compared with that of daidzein, a slowly disappearing flavonoid, in 5 men and 5 women. Subjects ingested 104 μmol of genistein and 62 μmol of daidzein (soy milk), 1549 μmol of naringenin and 26 μmol of hesperetin (grapefruit juice), and 381 μmol of quercetin (onions) in three test meals, each separated by 1 week. Blood and urine samples were collected over 24 h after each test meal. Plasma flavonoid concentrations ranged from 0.01 to 1 μM. The apparent absorption, expressed as percentage of ingested dose excreted in urine, was significantly less for naringenin (3.2 ( 1.7%), genistein (7.2 ( 4.6%), hesperetin (7.3 ( 3.2%), and quercetin (5.6 ( 3.7%) compared with daidzein (43.4 ( 15.5%, p = 0.02). These data affirmed the hypothesis that the 5,7,40-OH of flavonoids limited apparent absorption of these compounds in humans.