1. The metabolism of theophylline was studied in the recently developed, precision-cut, liver slice system. Metabolism of theophylline by rat and human liver slices increased over a 6 h incubation period. 2. Rat liver slices produced 1,3-dimethyluric acid, 1-methyluric acid, and uric acid. Human liver slices produced the same metabolite, as well as 3-methylxanthine. 3. Liver slices and microsomes obtained from the Aroclor-1254 pretreated rats metabolized theophylline at a 10-15-fold greater rate than those obtained from control rats. 4. When theophylline was administered orally to the control and Aroclor-1254 pretreated F-344 rats, the same metabolites were present in the urine as were produced in both in vitro systems. Much less theophylline and more metabolites were found in the urine of the Aroclor-1254 pretreated rat. 5. This study demonstrates that precision-cut slices maintained in the roller culture system can serve as a reliable in vitro method to assess the metabolism of xenobiotics.