The pineal gland and its major product melatonin have a key role in conveying the environmental photoperiodic stimuli that impinge upon the mammalian reproductive axis. The brain, especially the medial preoptic and suprachiasmatic areas are thought to be the main sites of melatonin's neuroendocrine activity. The responsiveness of the mammalian reproductive system to the hormone is dependent on age, on the prevailing cyclical stage and on the circadian time. The existence of specific 125I-melatonin binding sites in synaptosomal fractions from rodent brain has recently been reported. The binding of 125I-melatonin is inhibited by melatonin and by the novel melatonin antagonist ML-23 but not by dopamine, serotonin or other structurally related compounds. The densities of 125I-melatonin binding sites at discrete brain regions vary significantly with age, circulating levels of steroid hormones or circadian time. These phenomena are compatible with the existence of melatonin receptors in the brain.