Dietary flavonoid intake has been reported to be inversely associated with the incidence of coronary artery disease. To clarify the possible role of tea flavonoids in the prevention of atherosclerosis, we investigated the effects of tea flavonoids on the susceptibility of low-density lipoprotein (LDL) to oxidative modification. In an in vitro study, catechins or theaflavins (25-400 mumol/L) were added to plasma and incubated for 3 h at 37 degrees C. Then, the LDL fraction was separated by ultracentrifugation. The oxidizability of LDL was estimated by measuring conjugated diene, thiobarbituric acid-reactive substances (TBARS), and lipid peroxides after cupric sulfate was added. TBARS and lipid peroxides in the supernates were also measured after incubation with macrophages. Catechins significantly (P < 0.01 by ANOVA) and dose-dependently prolonged the lag time before initiation of oxidation. Among the catechins, epigallocatechin gallate exerted the most marked effect, prolonging the oxidation lag time more than vitamin E at the same molar concentration. Theaflavins exerted stronger inhibitory effects than catechins. Macrophage-mediated LDL oxidation was also inhibited by adding these tea flavonoids to the plasma samples. In an in vivo study, 14 healthy volunteers consumed 750 mL black tea/d for 4 wk. After the subjects had consumed tea for 4 wk, the lag time before LDL oxidation was significantly (P < 0.01) prolonged from 54 to 62 min. This minor prolongation occurred despite much lower plasma flavonoids than were used in vitro. No significant change was observed in eight control volunteers. LDL exposed to tea flavonoids in vitro or in vivo reduced oxidizability. We speculate that tea flavonoids may have a role in ameliorating atherosclerosis.