Elimination of nicotine by isolated rat livers was increased eightfold after pretreatment with phenobarbital (PB) as an inducer of cytochrome P-450 while it was only marginally influenced after pretreatment with 5,6-benzoflavone (BF) as an inducer of cytochrome P-448. Initial rates of cotinine formation were enhanced in the same order of magnitude in PB-induced livers. The 14C-nicotine-derived radioactivity excreted into bile within 2 h ranged between 6 -17% of the dose with only 2.7 fold higher values after PB pretreatment compared to controls.