In population studies, high intakes of coffee are associated with raised concentrations of plasma homocysteine, a predictor of risk of cardiovascular disease. Chlorogenic acid is a major polyphenol in coffee; coffee drinkers consume up to 1 g chlorogenic acid/d. OBJECTIVE: We studied whether chlorogenic acid affects plasma total homocysteine concentrations in humans. For comparison we also studied the effects of black tea rich in polyphenols and of quercetin-3-rutinoside, a major flavonol in tea and apples. DESIGN: In this crossover study, 20 healthy men and women ingested 2 g (5.5 mmol) chlorogenic acid, 4 g black tea solids containing approximately 4.3 mmol polyphenols and comparable to approximately 2 L strong black tea, 440 mg (0.7 mmol) quercetin-3-rutinoside, or a placebo daily. Each subject received each of the 4 treatments for 7 d, in random order. RESULTS: Total homocysteine in plasma collected 4-5 h after supplement intake was 12ø1.2 micromol/L; 95␌I: 0.6, 1.7) higher after chlorogenic acid and 11ø1.1 micromol/L; 95␌I: 0.6, 1.5) higher after black tea than after placebo. Total homocysteine in fasting plasma collected 20 h after supplement intake was 4ø0.4 micromol/L; 95␌I: 0.0, 0.8) higher after chlorogenic acid and 5ø0.5 micromol/L; 95␌I: 0.0, 0.9) higher after black tea than after placebo. Quercetin-3-rutinoside did not significantly affect homocysteine concentrations. CONCLUSIONS: Chlorogenic acid, a compound in coffee, and black tea raise total homocysteine concentrations in plasma. Chlorogenic acid could be partly responsible for the higher homocysteine concentrations observed in coffee drinkers. Whether these effects on homocysteine influence cardiovascular disease risk remains to be established.