Rats were treated with nitrogen-containing phenanthrene (3,4-, 5,6-, or 7,8-benzoquinoline) or anthracene (acridine or quinacrine) derivatives at a dose of 75 mg/kg, daily for 3 days. The hepatic drug metabolizing enzyme response ranged from no induction (quinacrine) through low (5,6-benzoquinoline), intermediate (acridine), and high (3,4-benzoquinoline) magnitude increases of only phase II enzymes, to induction of both phase I and phase II enzymes (7,8-benzoquinoline). The phase I enzyme response of 7,8-benzoquinoline was an induction of CYP1A. All three benzoquinolines, but neither anthracene derivative, elevated NAD(P)H quinone oxidoreductase activity. A similar pattern but of lesser magnitude was seen with glutathione S-transferase activity. 3,4-Benzoquinoline was the only agent to significantly increase microsomal epoxide hydrolase activity (2,3-fold). Both 3,4- and 7,8-benzoquinoline increased UDP-glucuronosyltransferase activity toward 4-nitrophenol (40% and 70%, respectively), but only the 3,4-isomer increased activity toward morphine (75%), diclofenac (75%), and testosterone (23%), and only the 7,8-isomer increased activity toward chloramphenicol (105%). 3,4-Benzoquinoline elevated the hepatic mRNA concentration of UGT2B1 but not UGT1*6. Acridine treatment increased UDP-glucuronosyltransferase activity toward morphine (47%), 1-naphthol (28%), testosterone (19%), and estrone (19%). Quinacrine failed to elevate any UDP-glucuronosyltransferase activity and depressed activities toward testosterone and estrone by 20%. This study shows that some tricyclic aromatic compounds containing a single heterocyclic nitrogen atom have the potential for use as chemoprotective agents based upon their ability to selectively induce only phase II enzymes.