Dark-cycle, night administration of the pineal hormone melatonin in drinking water to aging mice (15 months of age) prolongs survival of BALB/c females from 23.8 to 28.1 months and preserves aspects of their youthful state. Similar results were seen in New Zealand Black females beginning at 5 months and C57BL/6 males beginning at 19 months. As melatonin is produced in circadian fashion from the pineal, we grafted pineals from young 3- to 4-month-old donors into the thymus of 20-month-old syngeneic C57BL/6 male recipients, and a 12% increase in survival was induced. Prolongation of survival was also seen on pineal transplant to the thymus in C57BL/6, BALB/cJ, and hybrid female mice at 16, 19, and 22 months. In all studies, the endogenous pineal of grafted mice was left in situ. Pineal grafted aged mice display a remarkable maintenance of thymic structure and cellularity. Preservation of T-cell-mediated function, despite age, as measured by response to oxazolone is seen. Other evidence suggests that melatonin and/or pineal-related factors could produce their effects through an influence on thyroid function. These data indicate that pineal influences have a place in the physiologic regulation of aging.