It is unknown which endocrine disruptors exert their effects on neuronal functions, particularly leading to behavioral alterations. To address this, we examined the effects of p-n-octylphenol, an endocrine disruptor, on rat behavior and cellular responses. Single intracisternal administration of p-n-octylphenol (87 nmol) into 5-day-old male Wistar rats caused significant hyperactivity at 4-5 weeks of age. The treated rats were about 1.5-fold more active in the nocturnal phase after administration of p-n-octylphenol than control rats. Immunohistochemical analyses revealed that p-n-octylphenol abolished immunoreactivity for tyrosine hydroxylase in the midbrain of 8 week-old rats, where terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL)-positive cells were also seen. Thus, this is the first demonstration that p-n-octylphenol certainly affected the developing brain, resulting in hyperactivity in the rat, most likely due to degeneration of mesencephalic tyrosine hydroxylase.