The reactions of caffeine's main metabolites [paraxanthine, theobromine, theophylline, and 1-methylxanthine] with •OH, •OCH3, •OOH, and •OOCH3, in nonpolar and polar environments, have been studied using the density functional theory. Different mechanisms of reaction have been taken into account and their relative importance on the antioxidant activity of these compounds has been assessed. The free radical scavenging activity of the studied metabolites was found to be excellent for •OH, moderate for •OCH3, and negligible for peroxy radicals. The results from the present work indicate that the antioxidant activity of caffeine in our body remains almost the same when metabolized to paraxanthine, theobromine, theophylline, and 1-methylxanthine, while it is increased after being metabolized to 1-methyluric acid. In addition, the polarity of the environment was found to affect the overall reactivity of the studied compounds, to influence the relative importance of the different mechanisms and channels of reaction, and to have negligible effects on the relative scavenging activity of the studied compounds (theobromine > paraxanthine ≈ theophylline ≈ 1-methylxanthine). The studied metabolites were found to be better scavengers in nonpolar media than in aqueous solution. © 2012 Wiley Periodicals, Inc.