The distribution of microsomal cytochrome P-450 isozymes 2, 4, 5, and 6 and the pulmonary FAD-containing monooxygenase was determined in 10 different anatomical regions of the respiratory tract using immunoblot analysis and enzymatic assays. Cytochrome P-450 isozymes 2 and 5 and the FAD-containing monooxygenase were detected by immunoblotting in all of the pulmonary and nasal samples, although levels in nasal tissues were generally much lower than those levels found in the lung. Cytochrome P-450 isozyme 4, which is generally not present in extrahepatic tissues, was detected in nasal ethmoturbinates and mucosa. Different isozymes of cytochrome P-450 appear to be responsible for the N-demethylation of benzphetamine in lung as compared with nasal tissues. Isozyme 2 is responsible for the N-demethylation of benzphetamine in the lung, whereas another isozyme, possibly isozyme 3a is responsible for N-demethylation in nasal tissues. The presence of isozyme 3a in nasal samples was indicated by the presence of high rates of aniline hydroxylation.