Somatostatin receptors on lactotroph cells of the anterior pituitary are positively regulated by estradiol. In the present work, we investigated whether estradiol regulation of somatostatin receptors also occurred in the female rat brain. <sup>125</sup>I-Tyr₀-DTrp<sub>8</sub>-somatostatin (<sup>125</sup>I-SRIF: 780 Ci/mM ) was used as a ligand. Female adult rats were ovariectomized and treated or not with estradiol benzoate (20 µg/day for 1 or 8 days). In female brains, <sup>125</sup>I-SRIF binding, as assessed by film radioautography, was high in the basolateral amygdala, CA1 field and dentate gyms of the hippocampus and locus coeruleus, moderate in the median habenula and deep layers all through the cortex. Castration or estradiol treatment did not modify <sup>125</sup>I-SRIF binding in these regions. By light-microscopic radioautography, a subpopulation of <sup>125</sup>I-SRIF-labeled cells was localized in the ventrolateral portion of the arcuate nucleus. Ovariectomy alone did not significantly affect the number and binding density of <sup>125</sup>I-SRIF-labeled cells in the arcuate nucleus. However, estradiol treatment in ovariectomized animals significantly increased both parameters. Along the estrus cycle, the number of <sup>125</sup>I-SRIF-labeled cells was not significantly modified but <sup>125</sup>I-SRIF binding density was significantly higher in proestrus as compared to diestrus I, diestrus II and estrus. These results demonstrate that brain <sup>125</sup>I-SRIF binding sites are positively regulated by estradiol only in the arcuate nucleus of the hypothalamus.