INTRODUCTION THE INTRODUCTION of reliable radioimmunoassay methods for measurement of prolactin (PRL) in human blood has made it possible to study the factors that regulate the secretion of this hormone and to demonstrate that PRL secretion is controlled by neural mechanisms. Although the only known physiological function of this hormone is the regulation of lactation, its occurrence in men as well as women, the marked changes in secretion brought about by stress (both physical and psychological) and the alterations associated. with sleep cycles suggest that prolactin may be important for other functions as well. It has long been recognized that the predominant effect of the brain on PRL secretion is inhibitory, mediated by one or more prolactin inhibitory factors (PIF). One ofthe known prolactin inhibitory factors is dopamine which is inhibitory when added to pituitaries in vitro as well as after administration to living animals including man. This substance has also been demonstrated in hypophysial-portal-blood, but its concentration has not been correlated with the state of PRL secretion. In addition, several laboratories have identified substances with PIF activity in hypothalamic extracts free of catecholamines, but the nature of this substance(s) is still unknown. More recently, a stimulatory pathway regulating PRL secretion which includes a serotonergic component and prolactin releasing factor (PRF) has been defined. Although TRH is a PRF, and indeed is as potent a stimulator of PRL as of TSH secretion, PRL and TSH levels, under many circumstances, are not altered concomitantly, thus indicating that TRH is not an important physiological regulator of PRL secretion. Moreover, evidence for the existence of PRF distinct from TRH is accumulating. Disturbances in PRL regulation are now among the most common clinical problems seen by the endocrinologist, and have been classified both by clinical aspects and also on the basis of the known pathophysiology of the conditions. The major categories are: (1) adenomas of the pituitary (both micro and macro), (2) hypothalamic disorder (either destructive or dysfunctional), (3) drug induced, (4) neurogenic and (b') secondary to hypothyroidism. The most difficult question observed clinically is to distinguish between dysfunctional hyperprolactinemia and that due to occult pituitary adenomas.