SUMMARYHypothalamic regulation of prolactin secretion in animals (mammals) and man appears to be similar, and no significant differences have yet been demonstrated. The hypothalamus contains neurotransmitters and polypeptides that can either inhibit or stimulate prolactin release, although the predominant influence under basal conditions is to inhibit prolactin release. Thus pituitary stalk section or placement of lesions in the basal tuberal region of the hypothalamus results in increased prolactin release and sometimes in initiation of lactation. Among agents in the hypothalamus that can inhibit prolactin release, the most important appear to be an as yet unidentified polypeptide prolactin release inhibiting factor (PIF) and dopamine. There is some evidence that dopamine may account for most, if not all, of the prolactin release inhibiting activity of the hypothalamus. Agents that increase dopamine activity, i.e. L‐dopa, monoamine oxidase inhibitors, etc., depress prolactin release. Acetylcholine also can inhibit prolactin release, but it appears to act via the catecholamines. Of the agents in the hypothalamus that stimulate prolactin release, the most important appear to be an as yet uncharacterized polypeptide prolactin releasing factor (PRF), thyrotropin releasing hormone (TRH) and serotonin. TRH is as effective in releasing prolactin as in releasing TSH, but under most physiological states, TSH and prolactin release do not occur together. Serotonin and its precursors, tryptophan and 5‐hydroxytryptophan, are powerful releasors of prolactin and have been shown to be involved in some physiological states in which prolactin is released, i.e. during suckling, stress, etc. Other agents in the hypothalamus that can stimulate prolactin release include GABA and some prostaglandins, but these have not yet been shown to be involved in physiological control of prolactin secretion. Exteroceptive stimuli that alter prolactin release act through the CNS and hypothalamus, but some hormones and drugs also can act directly on the pituitary to promote or depress prolactin rele