The response of rat lung and liver ornithine decarboxylase (ODC) and aryl hydrocarbon hydroxylase (AHH) activities and lung benzo(a)pyrene (BP) metabolism was studied after exposing the rats to cigarette smoke. A close analysis of the time curves for ODC and AHH activities in rat lung and liver after a single exposure to cigarette smoke resulted in no clear correlation between the two parameters. Prolonged treatment (10 days) produced an increase in pulmonary ODC activity; hepatic ODC activity was unaffected. 10-day treatment was ineffective in raising AHH activity above values observed after a single treatment. BP metabolism, as determined in isolated perfused lungs by the appearance of organic- and water-soluble metabolites in the perfusion medium, the amount of covalently bound metabolites in lung tissue and the disappearance of unchanged 3-H BP from the perfusate, was markedly increased in response to cigarette smoke treatment. The data presented indicate that induction of AHH activity and increased metabolism of BP do not necessarily require a pre-existing increase in ODC activity.