Very little is known about the expression and function of the HOX and HOX-cofactors genes in mammalian oogenesis. The aim of the present study was to determine the expression of PBX and PREP-1 gene products in the mouse ovary and their localization to particular ovarian compartment, specifically the oocyte-containing ovarian follicle. Immunocytochemical analysis demonstrated that PREP-1 was present in both granulosa cells and oocytes. PREP-1 was found in the nucleus in primary oocytes, but in the cytoplasm of fully-grown oocytes; in granulosa cells, however, PREP-1 was always localized to the nuclei. No PREP-1 immunoreactivity was found in corpus luteum, theca or stroma. PBX-1 was found in the cytosol of the oocyte, while PBX-2 expression was mostly restricted to the nuclei of granulosa cells. In addition, PBX-2 was also found in the nucleus of primary oocytes. Since PREP-PBX complexes act in vivo in conjunction with HOX transcription factors, we have used RT-PCR to identify HOX genes expressed in the ovary. This analysis identified transcripts for six HOX genes (A5, A9, B6, B7, C6 and C8) and two more TALE cofactors (PREP2 and Meis2). Thus, a number of HOX and HOX cofactor genes are expressed in the mammalian ovary. The restricted expression pattern for PBX-1 and PBX-2 and the changes in expression and localization of PREP-1 in the oocyte and granulosa cells suggest a previously unsuspected involvement of these transcription factors in oocyte maturation and development, as well as in granulosa cell differentiation.