The effect of dose size on the metabolism of trans-anethole was investigated in rodents over the dose range 0.05-1500 mg/kg. trans-[methoxy-14C]Anethole was administered to female Wistar rats by gavage and to male CD-1 mice by ip injection. Urine, faeces and 14CO2 in expired air were collected and their 14C content was measured. Urinary metabolites were separated as described by Sangster et al. (Fd Chem. Toxic. 1984, 22, 695) and quantitated by radioHPLC and TLC. The major route of metabolism of trans-anethole in rodents is via oxidative O-demethylation and the importance of this route was found to decrease with increasing dose from 56 and 72% of the dose at 0.05 mg/kg to 32 and 35% of the dose at 1500 mg/kg in rats and mice, respectively. Over this dose range the elimination of 14C-labelled urinary metabolites increased significantly in both species. There was a species-specific regioselectivity in the side-chain oxidation of anethole. The rat favoured the epoxidation route, resulting in the elimination in the urine of two 1-(4'-methoxyphenyl)propane-1,2-diol isomers, elimination of which together rose from 2 to 15% of the dose over the dose range studied. In contrast the mouse favoured omega-oxidation, yielding cinnamyl compounds and 4-methoxybenzoic and 4-methoxyhippuric acids, the elimination of the latter two rising from 10 to 42% of the dose over the dose range studied. The species differences in metabolism, and the significance of the effect of increasing dose on the metabolic route are discussed with reference to the guidance these results could give in the assessment of the risk to man from dietary exposure to trans-anethole and related compounds.