It has been proposed that brain catalase plays a role in the modulation of some psychopharmacological effects of ethanol. The acute administration of lead acetate has dcmonstrated a transient increase in several antioxidant cell mechanisms, including catalase. In the present study, we investigated the effects of acute lead acetate administration on ethanol‐induced behavior, brain catalase activity, and the relation between both effccts. Lead acetate (100 mgkg) or saline was injected intraperitoneally in mice. At different intervals of time (1.3, 5, 7, 9, or 11 days) after this treatment, ethanol (2.5 g/kg) was injected intraperitoneally and the mice were placed in open field chambers. Results indicated that the locomotor activity induced by ethanol was significantly increased. Maximum ethanol‐induced locomotion increase (70% more activity than control animals) was found in animals treated with lead acetate 7 days before ethanol administration. Total brain catalase activity in lead‐pretreated animals also showed a significant induction, which was maximum 7 days after lead administration. A significant correlation was found between both effects of locomotor and catalase activity. In a second study, the effect of lead administration on d‐amphetamine (2.0 mg/kg) and tert‐butanol‐ (0.5 g/kg) induced locomotor activity was investigated. Lead acetatc treatment did not affect the locomotion induced by these drugs. These data suggest that brain catalase is involved in cthanol's effects. They also provide furthcr support for the notion that acetaldehyde may be produced directly in the brain via catalase and that it may be a factor mediating some of ethanol's central effects.