The effects of chronic melatonin treatment on glucocorticoid binding sites in hippocampus, hypothalamus and pituitary were investigated in rats, subjected to long-term manipulation of circulating corticosterone concentrations. 2. Melatonin treatment decreased the affinity of glucocorticoid receptors. 3. The effect of melatonin was apparent in the presence of normal or enhanced systemic corticosterone levels, but not in long-term adrenalectomized animals.