Influenza remains a major cause of illness and death in elderly people despite current vaccination programs. One factor is an immunization failure rate in the elderly that may be as high as 50%. To test whether administration of thymosin α 1 would result in greater antibody production, we administered it (900 μg/m2 subcutaneously twice weekly for eight doses) in conjunction with the 1986 trivalent influenza vaccine. Ninety men (65—99 years old, mean age 77.3 years) were randomized double-blind to receive thymosin α1, or placebo by the same schedule; the sera from 85 of these men were acceptable for analysis. The two groups were similar with respect to underlying disease, medications, and age. No toxicity was observed in either group. Antibody response rate was defined as a four-fold rise in antibody titer over 3—6 weeks following vaccination and was measured by an enzyme-linked immunosorbent assay (ELISA). Analysis was performed on treatment groups and subgroups divided by the mean age: the older group consisted of subjects aged 77 years and older, and the younger group those aged from 65—76 years. Baseline and change in absolute antibody levels were compared by t test and using age as a continuous variable by multiple regression analysis. The response was greater in the thymosin α1 treatment group at 6 weeks compared to the placebo group (P = .023), and this difference in absolute amount of antibody produced could be attributed to the greater response to vaccine in the older thymosin α1 treated subjects (P = .039) as no difference was observed between the younger treatment groups, or between the older thymosin α1 treated subjects and the younger subjects. The ability of elderly men receiving thymosin α1 treatment to produce antibody to vaccine similar to their younger counterparts may be of clinical importance.