The effect of acute ethanol administration on pentylenetetrazole-induced c-fos expression in rat brain was studied. Pentylenetetrazole induced the rapid and transient expression of c-fos mRNA in rat brain. Maximal induction at a dose of 30 mg/kg was detected within 30 min and persisted for 60 min. Thereafter c-fos gene expression decreased to control levels by 180 min. No increase in c-fos mRNA was evident at doses of pentylenetetrazole less than or equal to 20 mg/kg, whereas maximal elevation was seen at 30 to 40 mg/kg. This action was inhibited by acute ethanol treatment (blood alcohol level greater than or equal to 100 mg/dl). Acute ethanol treatment alone had no effect on c-fos gene expression.