Gene expression can be regulated by chromatin remodeling induced by the opposing actions of histone acetyltransferases and histone deacetylases (HDAC). HDAC inhibitors are considered putative anti-cancer drugs, but may also alter gene expression in the brain. Valproic acid (valproate; VPA), a drug used for treatment of bipolar disorder, has been characterized as a HDAC inhibitor. In neuronal cultures, VPA increases the expression of 5-lipoxygenase (5-LOX). Here we show that in vivo treatment of mice with intraperitoneal VPA injections increases the acetylation of histone H3 and the content of 5-LOX immunoreactive protein in the hippocampus. Since the extent of 5-LOX expression may alter mouse behavior, we suggest that VPA-altered chromatin remodeling and 5-LOX expression in the brain may be functionally important.