The pineal gland with its effects on immune system and free radicals may have a role on aging process. In this study, we investigated the effects of melatonin (10 mg/kg/d, s.c. for 7 days), the main secretion of the pineal gland, on the humoral immune responses of aged and young male Wistar rats. Eighteen aged (28 months old; 6 in control group and 12 in melatonin group) and 25 young (9 months old; 10 in control group and 15 in melatonin group) rats were given 4 x 10(8) sheep erythrocytes i.p. in order to evoke humoral immune responses. After a booster injection at the end of a period of three-weeks following the last melatonin injection, IgM and IgG1 levels were measured. Melatonin was found to increase IgG1 and IgM responses of aged rats when compared to controls (p = 0.049 and p = 0.007), respectively. In the young rats, while the IgG1 levels of control group were significantly higher than that of the melatonin group (p = 0.021), IgM levels were not significantly different (p = 0.563). It is concluded that exogenous melatonin may augment the depressed humoral immune responses seen aged rats.