DNA methylation regulates gene expression. Neuronal 5-lipoxygenase expression increases during aging and during the proliferation of immature rat cerebellar granule neurons. In these cultures, we investigated the effects of hypomethylating agents 5-aza-2'-deoxycytidine (AdC) and valproate on 5-lipoxygenase mRNA. Both drugs increased 5-lipoxygenase mRNA in proliferating cells; only valproate was effective in differentiated neurons. We propose that neuronal 5-lipoxygenase expression can be affected by aging-altered DNA methylation and by hypomethylating drugs, such as the anticonvulsant valproate.