Male, C57BL mice, Sprague-Dawley rats and Hartley guinea pigs were given daily exposure to either mainstream or sidestream whole smoke from University of Kentucky Reference cigarette, 2R1, for 16 weeks. Pulmonary aryl hydrocarbon hydroxylase (AHH) activity was assayed in lung tissue 9000 g supernatants by measuring the conversion of [3H]benzo[alpha]pyrene to its various metabolites. Both mainstream as well as sidestream smoke exposure increased the pulmonary AHH activity by approximately 3-4-fold over room and sham control rats and mice, but not guinea pigs. The magnitude of AHH induction in sidestream- and mainstream-exposed animals was similar, even though the dose of smoke particulates received by rats and mice in sidestream-exposed groups was significantly less than the amount inhaled by their corresponding mainstream-exposed groups. The data suggest that like mainstream, the sidestream cigarette smoke is also capable of inducing pulmonary AHH in responsive animal species.