The Ets gene family codes for transcription factors containing a conserved DNA binding domain: the Ets-binding domain. The proto-oncogene c-ets1 is highly expressed in lymphoid organs and in developing mesodermal-originating structures. We studied c-ets1 gene expression in the developing rat hypothalamo-hypophyseal system, using in situ hybridization on paraformaldehyde-fixed frozen sections. At embryonic day 12 (E12) and E13, cells synthesizing c-ets1mRNA are found in the neural tube where they form small, heavily labeled strand-like and punctate structures; positive mesenchymatous cells, corresponding to the surface capillary network, surround the brain and hypophysis. C-ets1mRNA is synthesized from E14 in the neural pituitary and E15 in the adenohypophysis, during angiogenesis; no c-ets1mRNA is detected in the avascular intermediate pituitary at any stage. Strand-like c-ets1mRNA labeling is intense from E14 to E21 in the diencephalon. This labeling is also detected during perinatal stages in the hypothalamic magnocellular nuclei, one of the most richly vascularized brain areas. In the rat hypothalamo-hypophyseal system, c-ets1 gene expression is maximal during fetal and perinatal stages and progressively decreases thereafter until adulthood. The spatio-temporal correlation observed between c-ets1 gene expression and blood vessel formation in the rat hypothalamus and pituitary suggests a role for c-ets1 in angiogenesis in this system.