Background: The consumption of unfiltered coffee, containing bioactive diterpenes, causes an increase in plasma homocysteine concentration. A slight increase in plasma homocysteine is also caused by large quantities of filtered coffee. Coffee terpenes also raise plasma glutathione in mice. Aim: To verify the effect of Italian-style coffee consumption on the plasma concentration of glutathione and homocysteine in healthy subjects. Methods: Twenty-two volunteers consumed five cups of coffee per day for I week and maintained their usual diet. Five subjects were enrolled as controls. The intervention trial was preceded and followed by seven coffee-free days. Results: Plasma glutathione increased by 16% (P < 0.05) on coffee consumption, and returned to the original concentration after the washout period. The increase in plasma homocysteine concentration (13% after 1 week of coffee intake) was not significant. No differences in glutathione or homocysteine concentration were observed in the control group. No variation of plasma hydroperoxide concentration was detectable. Conclusions: A coffee intake regimen, representing the average consumption of coffee drinkers in Italy, increased the plasma concentration of glutathione, but no significant increase in the plasma homocysteine concentration was detected.