Inbred strains of mice have been classified as aromatic hydrocarbon responsive or nonresponsive depending upon whether the parenteral administration of these substances increases hepatic aryl hydrocarbon hydroxylase (AHH) activity. Aromatic hydrocarbon responsiveness is controlled by genes at a small number of loci. Using 3-methylcholanthrene as inducing agent, strains A/J, C3H/HeJ, and C57BL/6J have been classified as responsive, whereas strains AKR/J, DBA/2J, and SWR/J are nonresponsive. Inhalation of cigarette smoke by both hepatic responsive and nonresponsive mice induces AHH activity in lung, but not in liver, stomach, small intestine, or kidney. The responsive strains have significantly higher levels of basal and induced AHH in the lung than do the hepatic nonresponsive strains. However, because of the especially low basal activity of AHH in lungs of hepatic nonresponsive strains, the ratio of AHH activity in animals treated with cigarette smoke to that in untreated animals is higher in nonresponsive than in responsive strains. AHH activity in lungs is fully induced within 6 to 12 hr after smoke inhalation and remains at the same level whether animals are treated 1 day or daily for 4 week;. AHH in lung returns to basal levels within 5 days after cessation of smoking.