Specific binding sites for rat CRF (r-CRF) have been characterized on rat anterior pituitary membranes. The binding of the radioiodinated analog of r-CRF (125I Tyr-r-CRF) was time, temperature, pH and protein dependent. No interaction was found with other neurohormones except with Arginine Vasopressin, but at supra physiological levels. Two classes of specific binding sites (high affinity and low affinity) for r-CRF were identified. Bilateral adrenalectomy provoked, since the 24th hour and up to 7 days, in addition of an increase of ACTH plasmatic levels, an abolition of the high affinity binding site; corticosterone treatment reversed these changes. This finding suggests that circulating glucocorticoids may control the anterior pituitary binding sites for CRF, either by a direct action on the anterior pituitary, or by a modulatory effect on hypothalamic CRF secretion.