Considerable controversy exists in the literature regarding the toxicity of coffee, including its possible carcinogenic and anticarcinogenic properties. This study reports on the reaction of 1,3,7-trimethylxanthine (caffeine) with the hydroxyl radical (.OH), as investigated by electron spin resonance (ESR) spin trapping. The .OH was generated by the Fenton reaction (Fe2+ + H2O2) as well as by the reaction of chromium(V) with H2O2. The results show that caffeine effectively scavenges .OH with a reaction rate constant of approximately 5.9 x 10(9) M-1 sec-1 that is comparable with those of other efficient .OH radical scavengers. ESR measurements provide evidence that a caffeine-derived oxygen-centred radical is formed in the reaction of caffeine with .OH and suggest a biochemical basis for the understanding of the reported anticarcinogenic properties of caffeine and related methylxanthine compounds.