The mechanism of hypercalcitoninemia associated with aging was investigated in male rats. To mimic some of the hormonal changes with aging, orchidectomized (Orch) and hyperprolactinemic rats were used to mimic the physiological status of aging. Orch and haloperidol-induced hyperprolactinemic rats aged 3, 8, and 17 months were infused with CaCl2 and then bled from a jugular catheter following the CaCl2 challenge. Rat thyroid gland was incubated with Locke's medium at 37 degrees C for 30 minutes. Compared with 8- and 3-month-old rats, 17-month-old rats exhibited the lowest levels of plasma testosterone and the highest levels of plasma prolactin (PRL) and calcitonin (CT). The release of CT in the thyroid glands in vitro was highest in 17-month-old rats. Orchidectomy decreased rat plasma CT and thyroid CT release in vitro. Hyperprolactinemic rats had higher levels of plasma PRL and CT compared with control animals. The release of thyroid CT in vitro was greater in hyperprolactinemic rats. These results suggest that the hypersecretion of CT in 17-month-old rats may be due in part to hyperprolactinemia.