Male Fisher rats were fed a diet ad lib. containing eugenol (4-allyl-2-methoxyphenol) to observe its effects on liver drug-detoxifying enzymes such as UDP-glucuronyltransferase (GT), UDP-glucose dehydrogenase (DH) and glutathione S-transferase (GST). Liver weights were not affected significantly by a diet containing 3% eugenol (w/w) for 13 weeks. The activities of GT of liver microsomes toward various xenobiotic substances such as 4-nitrophenol, 1-naphthol, 4-hydroxybiphenyl and 4-methylumbelliferone were enhanced by dietary administration of eugenol, but the activity of GT toward its endogenous substrate, bilirubin, was not changed. Dose-response relationships between the enhancement of GT activities toward these xenobiotics and the dose of eugenol were observed. The induced higher activities of GT toward these xenobiotics were maintained during 13 weeks of eugenol treatment. Similar results on DH and GST activities in the liver cytosol were obtained by dietary administration of eugenol, while no effect on cytochrome P-450 content in the liver microsomes from the rats fed the eugenol diet was observed during 13 weeks. These results suggest that the intracellular content of the active intermediates of various drugs or carcinogens would be reduced by this specific enhancement of drug-detoxifying enzymes in the liver of rats given a diet containing eugenol, as previously described for a diet containing 2(3)-tert-butyl-4-hydroxyanisole (BHA) [Y-N. Cha and H. S. Heine, Cancer Res. 42, 2609 (1982)].