The regulation of estrogen (ER) and progestin receptor (PR) mRNA and protein by their cognate hormones was examined in the hypothalamus and pituitary of steroid treated monkeys. Rhesus macaques (Macaca mulatta) were ovariectomized and hysterectomized (spayed) and implanted with Silastic capsules containing estradiol 17 (E) or progesterone (P). Steroid regulation of ER and PR mRNA levels in the hypothalamus and pituitary was examined with in situ hybridization (ISH). In the hypothalamus, ER and PR immunodetectable proteins were also examined in nearby sections. In the pituitary, mRNA levels were compared to previous ER and PR protein analysis of identically treated animals. E treatment induced PR mRNA in the medial basal hypothalamus and pituitary. Supplemental P treatment had no effect on PR mRNA levels in the hypothalamus, but markedly reduced PR mRNA in the pituitary. There was excellent agreement with PR protein detection by immunocytochemistry (ICC). E treatment had no effect on ER mRNA in the hypothalamus or pituitary. Supplemental P treatment decreased ER mRNA in the ventromedial nucleus (VMN), but not in the arcuate nucleus or in the pituitary. There was agreement between ER mRNA and ER protein in these areas. In summary, there is cell specific regulation of PR by P in the hypothalamus and pituitary wherein P downregulates PR in the pituitary without affecting ER. However, P has no significant effect on PR expression in the hypothalamus even though P decreases ER in the VMN. Although these observations suggest diverse cell specific regulatory mechanisms, they are consistent with ER and PR mediated physiological events such as prolactin secretion and sexual behavior.