The pineal nonapeptide hormone arginine vasotocin (AVT) is synthesized by the ependymal cells of the pineal recess and subcommissural organ and stored in so far undefined cells of the pineal gland proper. AVT is first released into the cerebrospinal fluid (CSF) and reaches the blood only secondarily after its absorption from CSF. It displays a diurnal rhythm in the pineal and CSF, suggesting its release into the CSF during the night in the dark. Melatonin represents its releasing hormone. AVT exerts both its endocrine and non-endocrine effects by a unique mechanism involving the activation of serotonin neurotransmission in the brain with resultant inhibition of release of hypothalamic releasing and inhibiting hormones and induction of sleep. It produces both its endocrine effects and sleep at concentrations equivalent to only several hundreds of molecules, being thus by far the most active hormone so far known. Midbrain raphe nuclei or some structures intimately correlated with these cell bodies, most contain the extremely sensitive and specific AVT receptors in the mammalian brain. In contrast with its natural analogues arginine vasopressin and oxytocin which are mainly blood hormones, AVT is a CSF hormone whose major if not the sole site of action is the brain itself.