BACKGROUND An elevated plasma concentration of total homocysteine is considered to be a strong risk factor for cardiovascular disease. Heavy coffee drinking has been related to high homocysteine concentrations in epidemiologic studies and in one experiment in which healthy subjects drank unfiltered, boiled coffee. OBJECTIVE Our goal was to determine whether daily consumption of paper-filtered coffee raises plasma concentrations of total homocysteine in healthy subjects. DESIGN Twenty-six volunteers (18-53 y of age) consumed 1 L/d of paper-filtered coffee brewed with 70 g regular ground beans or no coffee for 4 wk each in a randomized, crossover design. RESULTS The mean (+/-SD) plasma concentration of total homocysteine in fasting blood was 8.1 +/- 1.8 micromol/L after abstention from coffee and 9.6 +/- 2.9 micromol/L after 3-4 wk of coffee drinking, a difference of 1.5 micromol/L (95% CI: 0.9, 2.1 micromol/L) or 18% (P: < 0.001). Coffee increased homocysteine concentrations in 24 of 26 individuals. Circulating concentrations of vitamin B-6, vitamin B-12, and folate were unaffected. CONCLUSION Drinking large quantities of paper-filtered coffee raises fasting plasma concentrations of total homocysteine in healthy individuals.