Binding of oestrone and oestradiol to a pituitary cytosol receptor was studied in ovariectomized sheep during the breeding season, during anoestrus and after oestradiol treatment during anoestrus. All sheep were ovariectomized 2 weeks before removal of the anterior pituitary. Oestrogen treatment consisted of the subcutaneous implantation of Silastic capsules containing oestradiol-17beta 3 weeks before ovariectomy. Association constants (KA) for oestrone and oestradiol and the concentration of binding sites for oestradiol varied with changes in reproductive state. Oestradiol bound more tightly and the concentration of available binding sites was lower during the breeding season than during anoestrus. The affinity of oestrone binding was less during the breeding season than during anoestrus, whilst the concentration of binding sites for this steroid did not change with changes in reproductive state. Treatment of anoestrous sheeep with oestradiol increased the KA for oestradiol and decreased the concentration of binding sites. However, no effect of oestradiol treatment was observed with regard to the KA or concentration of binding sites for oestrone. The results suggest that either the pituitary oestrogen cytoplasmic receptor undergoes a conformational change during the breeding season causing oestradiol to be more tightly bound or the onset of the breeding season is accompanied by the appearance of a new receptor which binds to oestradiol with greater affinity. Oestradiol treatment of anoestrous sheep mimics this change.