Circulating immunoreactive alpha-interferon in elderly individuals was 0.139 +/- 0.042 ng/ml in males and 0.111 +/- 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 less than 0.01), but higher compared with the values found in disease states including rheumatoid arthritis (p less than 0.0025). There was no correlation between circulating alpha-interferon and bone mass indices, such as bone mineral content or quantitative computed tomography values, in these elderly individuals. Circulating alpha-interferon was, however, significantly increased in senile osteoporotic patients after 2 months of treatment with 1 alpha-hydroxyvitamin D3 or calcitonin, whereas it was unaltered in patients receiving ipriflavone or in nonosteoporotic individuals without medication. These findings indicate that circulating alpha-interferon, which is highest in young adults, declines with aging. It appears that circulating alpha-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 alpha-interferon, it is possible that bone and cellular metabolism related to vitamin D3 may be contributing factors for the maintenance of circulating alpha-interferon.