Circulating immunoreactive α-interferon in elderly individuals was 0.139 ± 0.042 ng/ml in males and 0.Ill ± 0.033 ng/ml in females at ages 70–79, and 0.120 ± 0.045 ng/ml in males and 0.105 ± 0.039 ng/ml in females at ages 80–89. These values were significantly lower than those in young adults (p < 0.01), but higher compared with the values found in disease states including rheumatoid arthritis (p < 0.0025). There was no correlation between circulating α-interferon and bone mass indices, such as bone mineral content or quantitative computed tomography values, in these elderly individuals. Circulating α-interferon was, however, significantly increased in senile osteoporotic patients after 2 months of treatment with 1 α-hydroxyvitamin D3 or calcitonin, whereas it was unaltered in patients receiving ipriflavone or in nonosteoporotic individuals without medication. These findings indicate that circulating α-interferon, which is highest in young adults, declines with aging. It appears that circulating α-interferon is maintained at a certain steady-state level in healthy elderly individuals. Although there was no apparent relationship between bone mass indices and circulating α-interferon, it is possible that bone and cellular metabolism related to vitamin D3 may be contributing factors for the maintenance of circulatin