Pulmonary metabolites of p-xylene, p-methylbenzyl alcohol (PMBA) and 2,5-dimethylphenol (DMP), were employed to investigate the divergent effects of p-xylene on pulmonary and hepatic metabolism. Rats were given PMBA, DMP, or 10% cremophore (control) ip daily for 3 days, and effects on hepatic and pulmonary microsomal metabolism were determined 12 hours later. Both PMBA and DMP mimic the decrease in pulmonary benzyloxyresorufin-O-debenzylase activity previously reported for p-xylene, but neither could account for the potent induction of cytochrome P450 in the liver. Only PMBA had a consistent effect on P450IIB apoprotein levels, decreasing them in both the liver and lung. These data suggest that PMBA may have a significant role in the inhibition of pulmonary P450 caused by p-xylene.