The influence of whole tobacco smoke or the gas phase from smoke on the pulmonary metabolism of [14C]benzo[a]pyrene was examined. [11C]Benzo[a]pyrene disappears from plasma-perfusing isolated rabbit lungs according to first-order kinetics. When these lungs are ventilated with freshly generated whole cigarette smoke, the slope of [14C]benzo[a]pyrene disappearance curves are altered dramatically; the amount of this alteration is dependent on the dose of smoke administered. If the particulate phase is filtered out of the smoke and the resulting gas phase is administered to the lung, relatively little effect is seen. These results suggest that the acute effect of whole smoke on benzo[apyrene metabolism by the isolated perfused lung is inhibition and that this effect is primarily due to the materials present in the particulate phase of smoke.