In both mammalian and insect models of ethanol-induced behavior, low doses of ethanol stimulate locomotion. However, the mechanisms of the stimulant effects of ethanol on the CNS are mostly unknown. We have identifiedtao, encoding a serine-threonine kinase of the Ste20 family, as a gene necessary for ethanol-induced locomotor hyperactivity inDrosophila. Mutations intaoalso affect behavioral responses to cocaine and nicotine, making flies resistant to the effects of both drugs. We show thattaofunction is required during the development of the adult nervous system and thattaomutations cause defects in the development of central brain structures, including the mushroom body. Silencing of a subset of mushroom body neurons is sufficient to reduce ethanol-induced hyperactivity, revealing the mushroom body as an important locus mediating the stimulant effects of ethanol. We also show that mutations inpar-1suppress both the mushroom body morphology and behavioral phenotypes oftaomutations and that the phosphorylation state of the microtubule-binding protein Tau can be altered by RNA interference knockdown oftao, suggesting thattaoandpar-1act in a pathway to control microtubule dynamics during neural development.