Estrogens play a significant role during mammalian brain development and are required for the masculinization of neuronal circuits involved in sex-specific behaviors and neuroendocrine functions. Cellular estrogen signalling is transmitted through nuclear estrogen receptors (ER) which are divided into two subforms: the ER-α as well as the recently cloned ER-β have been demonstrated in the hypothalamus. In the present study, we have analyzed the sex-specific expression of ER-β mRNA in the pre- and postnatal mouse hypothalamus/preoptic region (Hyp/POA) by semiquantitative RT-PCR. The ER-β mRNA was detectable as early as embryonic day (E) 15 in the diencephalon of both sexes. In males, levels of mRNA expression in the Hyp/POA increased until birth and remained high throughtout postnatal (P) development, whereas in females, such an increase was not observed. Significantly higher mRNA levels were detected in the male Hyp/POA from E17 until P15. Perinatal sex differences in ER-β mRNA expression coincide with higher estrogen-forming rates in the male Hyp/POA. At present, no direct evidence is available which demonstrates that estrogen signalling through ER-β is involved in brain development. However, data from our and other studies suggest a potential role for this signal transduction pathway for brain differentiation.