The effect of polycyclic aromatic hydrocarbons on theophylline clearance was examined in six inbred mice strains. The DBA/2 and SJL strains were nonresponsive to this treatment, whereas C3H/HeJ, C57BL/6, BALB/c, and A/J strains were responsive. In the responsive strains, the total body clearance increased by a factor of 2.3 to 3.4, apparently due to a general induction of all metabolic pathways. The production of 1,3-dimethyluric acid was not increased in the C57BL/6 strain. The variation in induction among responsive strains appeared to be primarily associated with the increase in the oxidation to 1,3-dimethyluric acid.