Maximal aniline hydroxylase and hexobarbital oxidase activities were evident in rats fed between 1 and 10 µl arachidonate/day whereas cytochrome P-450 was at a maximum between 10 and 30 µ\l day. NADPH cytrochrome C reductase and cytochrome P-450 reductase activities were unaltered in a significant way by this essential fatty acid. Cytochrome P-450 of microsomes from rats fed increasing quantities of menhaden oil tended to increase but aniline hydroxylase was depressed in both fat-free fed rats and those given 100 αl/day and hexobarbital oxidase was depressed only in livers from rats fed the fat-free diet. Neither cytochrome P-450 reductase nor NADPH cytochrome C reductase was affected by menhaden oil ingestion. Glucose-6-phosphate dehydrogenase activity was elevated in nearly all doses of arachidonate and menhaden oil below 100/4/day. It appears that dietary fatty acids such as arachidonate and docosahexaenoate (menhaden oil) are involved in the synthesis or maintenance of hepatic drug metabolizing enzym