It has been demonstrated that cytokine activities are under neuroendocrine control, recently mainly exerted by the pineal gland through the circadian secretion of its main hormone melatonin (MLT). It is mainly released during the night, but at present it is still unclear which relation exists between MLT and the circadian secretion of cytokines. This study was performed to evaluate the circadian secretion of IL-2, IL-6, IL-10 and IL-12 in relation to that of MLT. The study included 10 healthy volunteers whose venous blood samples were collected at 8 a.m., noon, 4 p.m., 8 p.m., 1 a.m. and 4 a.m. The mean levels of MLT were significantly higher during the night than during the light phase of the day. Similarly, IL-2 mean levels significantly increased during the night. IL-6 mean values were higher during the light period of the day without, however, any significant differences with respect to the nocturnal mean levels. Finally, no substantial circadian variation was seen in IL-10 and IL-12 mean concentrations. These results show that IL-2 secretion increases during the night, concomitantly to that of the pineal hormone MLT, whereas there is no evidence of a circadian secretion for the other cytokines. Since the pineal gland has been proven to stimulate IL-2 endogenous production, the nocturnal increase in IL-2 blood concentrations could depend at least in part on the promoting action of MLT, whose release increases during the dark period of the day.