The influence of whole tobacco smoke or the gas phase from smoke on the metabolism of [14C]benzo[a]pyrene was e xamined using the isolated perfused rabbit lung model. Fresh whole tobacco smoke mixed with the air ventilating the perfused lung produces an immediate and dose related decrease in the metabolism of [14C]benzo[a]pyrene. The metabolites of [14C]benzo[a]pyrene, diols, quinones, phenols and polar compounds are generally decreased in quantity. At the lowest level of smoke administered the percentage of BP-7,8-diol produced is increased dramatically. The results indicate that one of the factors contributing to the carcinogenicity of tobacco smoke may be its ability to produce an immediate alteration in the pulmonary metabolism of polycyclic aromatic hydrocarbons.