Introduction THE PINEAL gland has received increasing interest from investigators during the past decade. As the pineal has become more intensively investigated, its involvement in the modulation of specific endocrine systems, in particular the gonadal system, has become more clearly delineated. Due to the obvious difficulty in obtaining human material with which to work, investigators by necessity have concentrated their efforts in determining pineal gland function by utilizing a number of subhuman mammals, primarily the rat and the hamster. This review will discuss the historical literature relevant to the pineal gland, the anatomy of the pineal gland including neural and vascular connections, and the histological appearance of the vertebrate pineal gland. The biologically active substances which have been identified within the pineal gland will be discussed, with particular emphasis on the synthesis of melatonin and the photoperiodic and hormonal modulation of melatonin synthesis. Evidence which is currently available concerning the effects of the pineal gland and melatonin on the gonadal system will be discussed in some detail; in addition some less well-known effects such as on the thyroid gland, adrenal gland and growth hormone secretion will also be discussed. The final portion of this review will involve a discussion of the role of the pineal gland in tumors, the different types of pineal tumors, and the clinical manifestations of these tumors, both neurological and endocrinological.