Forty autopsy pituitaries were studied to elucidate the histology, immunocytology and ultrastructure of pars tuberalis in subjects with normal and abnormal endocrine homeostasis. Pars tuberalis consisted mainly of gonadotrophs interspersed with few corticotrophs and thyrotrophs, histologically resembling those of pars distalis. Somatotrophs and lactotrophs were not identified. There were no histologic differences attributable to age or sex. In cases of glucocorticoid excess, pars tuberalis corticotrophs showed Crooke's hyalinization. Following castration or hypophysectomy, pars tuberalis gonadotrophs exhibited more intense immunostaining for FSH and LH than did normals. Ultrastructural analysis revealed gonadotrophs and corticotrophs showing no evidence of active secretion; immunoelectron microscopy demonstrated FSH, LH and ACTH in secretory granules. By light microscopy, squamous nests, often identified in pars tuberalis, were positive for immunoreactive keratin; cells at their periphery contained FSH, LH or ACTH, indicating derivation of nests by squamous metaplasia from gonadotrophs and corticotrophs. By electron microscopy, clusters of epithelial cells containing desmosomes and tonofilaments were surrounded by granulated gonadotrophs. Human pars tuberalis cells represent mainly a subpopulation of gonadotrophs possessing all organelles required for synthesis and storage of hormones but showing ultrastructural features of functional inactivity; the reasons for this inactivity and for the formation of squamous nests remain unexplained.