It has not been known which endocrine disruptors exert their effects on neuronal functions, particularly leading to behavioral alterations. To address this, we examined the effects of p-nitrotoluene, an endocrine disruptor, on rat behavior and gene expression. Single intracisternal administration of p-nitrotoluene (ca. 10 microg) into 5-day-old male Wistar rats caused significant hyperactivity at 4-5 weeks of age. They were about 1.4-fold more active in the nocturnal phase after administration of p-nitrotoluene than control rats. Based on DNA array analyses, p-nitrotoluene decreased more than two-fold the levels of gene expression of the mesencephalic dopamine transporter at 8 weeks old. Thus, it was demonstrated for the first time that p-nitrotoluene definitely affected the developing brain, resulting in hyperactivity in the rat.