High-affinity progestin binding sites were found in the brain and pituitary of the female South African clawed frog, Xenopus laevis. Cytosol progestin receptors in the hypothalamus-preoptic area and pituitary were increased in number by estradiol treatment in ovariectomized frogs. The telencephalon also contained high-affinity binding sites, but the concentration was not affected by estrogen priming. Autoradiographic analysis of the distribution of the synthetic progestin 3H-R5020 revealed some lightly labeled cells in the anterior preoptic area and ventral infundibulum of ovariectomized animals. After estrogen priming, many heavily labeled cells were observed in the following areas: ventrolateral striatum and amygdala, anterior preoptic area, ventral infundibular nucleus, laminar nucleus of the torus semicircularis, and anterior pituitary. The areas in which dense accumulations of 3H-R5020 labeled cells were found after estrogen treatment are a subset of areas known to contain estrogen binding sites. The induction of progestin receptors by estradiol may be related to the requirement for both estrogen and progestin to elicit female sexual behavior in this species.