Influenza vaccine efficacy is reduced among adults over age 65 and a significant number of vaccinated elderly may remain susceptible to influenza virus infection. The effect of moderate exercise training on the immune response to influenza immunization was evaluated in this study. Twenty-seven adults >or=age 64 were assigned to an exercise group (n= 14) or a control group (n = 13). The subjects exercised at 65-75% heart rate reserve (HRR), 25-30 min, 3 days per week, for 10 months. Controls did not change activity. Subjects were immunized with trivalent influenza vaccine before and after the exercise intervention. After the exercise intervention, exercisers exhibited a greater mean fold increase (MFI) in antibody titer to influenza A/New Caledonia/20/99 (H1N1) and A/Panama/2007/99 (H3N2) than controls, and a greater Granzyme B activity to A/Panama/2007/99 than controls. These findings suggest that exercise may enhance the mean fold increase in antibody titer in response to influenza immunization if the influenza antigen was contained in the previous year's vaccine.