The effect of caffeine on the development of hepatic tumors induced by 2-acetylaminofluorene (2-AAF) was studied in 6-week-old male ACI rats. Rats in group 1 were fed a diet containing 0.02% 2-AAF for 18 weeks and then basal diet for 15 weeks with normal drinking water throughout. Animals in group 2 received a diet containing 0.02% 2-AAF and a solution of 0.2% caffeine as their drinking water for 18 weeks, followed by basal diet and caffeine-free water. Rats in group 3 received drinking water containing 0.2% caffeine for 18 weeks. Rats in group 4 were given a basal diet and water freely and served as controls. The experiment was terminated after 33 weeks. Both the multiplicity, i.e. the number of tumors per rat, and the size of tumors were less (P less than 0.001 in the former case, by Student's t-test) in group 2 than in group 1. Thus, the induction of tumors of the liver by 2-AAF was suppressed by the administration of caffeine.