Apurinic/apyrimidinic endonuclease (APE; also referred to as Ref-1) repairs oxidative damage to DNA and regulates the redox state of DNA binding proteins. This later property influences the ability of DNA binding proteins, which include Fos and Jun, to bind to AP-1 complexes. Since DNA binding proteins may play important roles in regulating neuronal activity in the hypothalamus, we examined the expression of APE in the hypothalami of rats. In situ hybridization studies revealed high levels of APE mRNA expression in the suprachiasmatic nuclei (SCN), supraoptic nuclei (SON) and paraventricular nuclei (PVN). Since the SCN are the site of a biological clock, we examined whether APE gene expression was regulated by the circadian cycle or by light. Quantitative in situ hybridization studies showed that APE mRNA levels remained constant over the circadian cycle and were not increased by light exposure at night. We also tested if APE expression was under osmotic control in the SON and PVN. Hypertonic stimulus, however, did not induce further expression of APE mRNA in either the SON or the PVN. These findings identify the SCN, SON and PVN as sites of high level APE gene expression. These data suggest that APE may play an important role in these structures either to facilitate DNA repair or DNA binding protein action.