The orphan receptor TR4, member of the nuclear hormone receptor family, is related to the orphan receptors TR2, COUP-TFI and ARP-1, and was originally cloned from the adult rat brain. The latter two orphan receptors have been implicated in central nervous system (CNS) development. To investigate a possible role for TR4 in brain development, expression of TR4 was studied in rat embryos. At embryonic days 14.5 and 19.5, high expression of TR4 was found in the CNS, while low expression was detected throughout the embryo. In postnatal rats, TR4 was mainly expressed in the hippocampus and cerebellum, resembling the expression pattern found in adult brain. These data show that like COUP-TFI and ARP-1, expression of TR4 becomes restricted to distinct areas. In adult brain, TR4 is predominantly expressed in granule cells of both hippocampus and cerebellum. The data suggest a possible role for TR4 during proliferation and maturation of brain structures.