SummaryAutoxidized linoleic acid (AL) having 800meq/kg of per oxide value and 1,700meq/kg of carbonyl value was given in repeated oral doses at a daily dose of 0 (control)-7.5ml/kg to male Wistar rats for 5 successive days. The effect of increasing AL dose on the drug-metabolizing system was investigated in rat liver microsomes and S-9 fractions. All the rats of a daily dose of 5.0-7.5ml/kg died after the third day of consecutive oral doses. The cytochrome P-450 and b5 contents, enzyme activities in electron transfer system, aminopyrin-N-demethylase activity and S-9 activity (metabolic activation of 2-acetylaminofluorene) in the drug metabolizing system changed essentially in a similar manner, that is, both the contents and the activities were increased by a small dose of AL, and were decreased by a large dose of AL. These results strongly supported the fi ndings in a previous report wherein we observed the periodical effect of AL dose on the drug-metabolizing system. Key Words autoxidized linoleic acid, microsome, cytochrome P-450, cytochrome b5, electron transfer system, drug-metabolizing activity, aminopyrin-N-demethylase, S-9 activity, membrane disorder There have been some incompatible findings on the effect of autoxidized oil on drug-metabolizing activity in rat liver microsomes under the respective experimental conditions (1, 2). Therefore, in our previous work (3), AL having 800meq/kg of peroxide value and 1,700meq/kg of carbonyl value was administered periodically for 1-15 days at a daily dose of 2.5ml/kg body weight to male Wistar rats, and the effect of AL on the drug-metabolizing system in rat liver microsomes was studied. The cytochrome P-450 and b5 contents were increased by consecutive oral doses of AL for 3-7 days, then the amount of cytochrome P-450 decreased gradually, but the b5 decreased slightly. Thus, after administration for 11-15 days, the cytochrome P -450 content was significantly lower, but the cytochrome b5 content was rather high 97