Twenty-two S12 preparations of surgical lung specimens obtained from smoker and non-smoker cancer patients were assayed to detect aryl hydrocarbon hydroxylase (AHH), dimethylnitrosamine demethylase (DMND), and glutathione-S-transferase (GST) activities, in both normal and neoplastic lung tissue from the same patients. Pulmonary fractions were also tested for their ability to activate some precarcinogens into mutagenic metabolites in the Ames test. Statistically significant differences were found for AHH and DMND activities between normal and neoplastic tissue of smoker patients. In addition, higher AHH activity in the neoplastic tissue of the smoker group was observed compared with that found in the non-smoker group. No differences were found for GST activity. All the lung S12 preparations were able to metabolize water-soluble bases and water-insoluble bases, derived from main-stream cigarette smoke condensate, into mutagenic agents in the Salmonella test system. However, S12 preparations from smoker group neoplastic tissues were more effective.