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Because aryl hydrocarbon hydroxylase (AHH) is considered to be responsible for the activation of benzo(a)pyrene and other polyaromatic hydrocarbons in cigarette smoke to carcinogens, it is important to examine CYP1A1 (AHH) activity in the determination of susceptibility to lung cancer. We investigated AHH activity in peripheral mitogen-treated lymphocytes in 108 lung cancer patients and 95 healthy control individuals. Non-induced AHH activity was detectable in all the samples. AHH inducibility (3-methyIcholanthrene-inducednon-induced AHH activity) showed a very wide interindividual variation as well as non-induced AHH activity. No significant associations were found between adjusted AHH activity and histologic type of tumor among lung cancer patients. Adjusted AHH inducibility of genotype C geometric mean and 95 confidence interval (CI); 15.56 and 11.69-20.71 in MspI polymorphism was significantly higher than those of the other two genotypes (P0.0001), while no significant difference was observed between genotypes A (4.76 and 3.82-5.93) and B (5.60 and 4.57-6.86). On the other hand, non-induced AHH activity of genotype ValVal (0.121 and 0.082-0.178 pmolmin106cells) in isoleucinevaline (He-Val) polymorphism was significantly higher than those of genotypes IleIle (0.042 and 0.034-0.052 pmolmin106cells) and IleVal (0.040 and O.O3O-O.O53 pmolmin106 cells) (P<0.0001). Even after controlling for age, cigarettes smoked per day and season of the year, high AHH inducibility (7.0 < versus 0 < ≤ 3.0 OR and 95 CI, 12.4 and 2.88-53.4) was an independent risk factor for lung cancer. The data indicate that high AHH inducibility may strongly associate With the Susceptibility to lung Carcinogenesis.