Melatonin is secreted by the pineal gland and exhibits a striking circadian rhythm in its release. Depending on the species studied some pituitary hormones also display marked circadian/seasonal patterns and rhythms of secretion. However, the precise relationship between melatonin and pituitary function remains controversial, and studies focusing on the direct role of melatonin in normal pituitary cells are limited to non-primate species. Here, adult normal primate (baboons) primary pituitary cell cultures were used to determine the direct impact of melatonin on the functioning of all pituitary cell types from the pars distalis. Melatonin increased GH and PRL expression/release in a dose- and time-dependent fashion, a response that was blocked by somatostatin. However, melatonin did not significantly affect ACTH, FSH, LH or TSH expression/release. Melatonin did not alter GHRH- or ghrelin-induced GH and/or PRL secretions, suggesting that melatonin may activate similar signaling-pathways as ghrelin/GHRH. The effects of melatonin on GH/PRL release, which are likely mediated through MT1 receptor, involve both common (AC/PKA/extracellular calcium-channels) and distinct (PLC/intracellular calcium-channels) signaling-pathways. Actions of melatonin on pituitary cells also included regulation of the expression of other key components for the control of somatotrope/lactotrope function (GHRH-, ghrelin- and somatostatin-receptors). These results show, for the first time in a primate model, that melatonin directly regulates somatotrope/lactotrope function, thereby lending support to the notion that the actions of melatonin on these cells might substantially contribute to the define daily patterns of GH and PRL observed in primates, and perhaps in humans.