Abstract To measure tissue specificity for specific progesterone binding, various tissues (liver, kidney, vagina, uterus, spleen, duodenum, heart) and serum were analyzed from proestrous hamsters. Of the tissues examined, only the uterus and vagina contained a protein in cytosol with the physicochemical properties of a progesterone receptor (Rp) (i.e. high binding affinity for progesterone, limited binding capacity, hormonal binding specificity, a 6–7 S sedimentation coefficient in low ionic medium). In contrast, the progesterone-binding component in kidney and liver cytosol appears to be CBG, based on its lower affinity for progesterone ( K A = 5–9 × 10 7 M −1) and its 4–5 S sedimentation coefficient. Progesterone binding was not detectable in serum or in cytosol fractions derived from heart, spleen or duodenum. Following ovariectomy, vaginal cytosol Rp levels decreased; but they rapidly increased to levels greater than those measured prior to ovariectomy in response to oestrogen replacement therapy. Treatment of these animals with progesterone, depleted Rp from the cytosol of uterus and vagina, whereas such treatment did not affect the level of the progesterone binder in liver or kidney. Thus, these results confirm the presence of specific Rp in hamster uterine cytosol, and establish that hamster vaginal cytosol contains Rp with physicochemical properties: consistent with those expected of a steroid receptor; similar, if not identical, to those of uterine Rp; and distinctly different from the progesterone binding components present in “nontarget” tissues.