The effect of aging on human humoral immunity was investigated by studying in vivo the relationship between influenza specific antibody responses and nonspecific vaccine-induced autoantibody responses in 32 independent, well-nourished older women volunteers (mean age 86 yr, range 74-97) and 23 young women volunteers (mean age 34 yr, range 23-46). Anti-influenza A/Taiwan/1/86(H1N1) antibody titers were determined by a hemagglutination inhibition test (HI-test), and serum anti-dsDNA antibodies were measured by ELISA prior to, 15, and 30 days after influenza vaccination. The mean postvaccination fold increase (FI) of the anti-influenza antibody response was significantly lower in elderly individuals as compared to younger individuals. In contrast, the mean anti-dsDNA autoantibody level measured 30 days after vaccination was significantly increased in older volunteers as compared to younger ones. There was a significant negative correlation between the level of the FI of the anti-influenza antibody response and the anti-dsDNA antibody response (r = -.441, p less than .01). Our results suggest that the altered influenza specific antibody response was associated with an age-related increase in autoimmunity in aging individuals.