The metabolism of benzo[a]pyrene (BaP) may be altered by xenobiotic compounds. The effects of p-xylene and ethanol on the lung metabolism of BaP were studied. p-Xylene was administered by ip injection at doses ranging from 0.1 to 1.0 g/kg (1:1 in soybean oil). Ethanol was administered po at 5 g/kg (40% w/v). Rats given p-xylene, ethanol, or p-xylene and ethanol were sacrificed 1 h after treatment. Additional time points of 15 min, 30 min, 4 h, and 24 h after p-xylene (1 g/kg) were examined. 3-Hydroxy-BaP (3-OH) formation was measured fluorometrically as aryl hydrocarbon hydroxylase activity (AHH) in lung microsomes. p-Xylene (1 g/kg) inhibited the formation of 3-OH BaP 40% at 15 min, 27% at 30 min, 43% at 1 h, and 39% at 4 h after treatment. Inhibition of AHH activity was still present 24 h after dosing (41%). AHH activity was inhibited 27% and 46% at 0.5 mg/kg and 1.0 mg/kg p-xylene (1 h), respectively, while the lowest dose (0.1 mg/kg) did not change activity. Analysis of the major metabolites of BaP by high-performance liquid chromatography (HPLC) demonstrated that the formation of 3-OH and 4,5-diol BaP were inhibited 32% and 50%, respectively, in lung microsomes prepared 24 h after a single injection of p-xylene (1 g/kg). None of the other metabolites analyzed were changed by p-xylene. Ethanol had no effect on 3-OH BaP formation during a 1-h treatment. A combined dose of ethanol and p-xylene moderately inhibited 3-OH BaP formation. These findings indicate that BaP detoxication (i.e., 3-OH formation) in rat lung is selectively inhibited by p-xylene but not ethanol. Ethanol appears to modify the inhibitory effect of p-xylene.