While influenza immunization significantly reduces the risk of pneumonia and associated deaths, vaccination of elderly only affords 30-50% protection against influenza disease. The purpose of this study was to: (1) evaluate the consistency of immune responses across multiple years in young and elderly; (2) determine the contribution of antibody and cell-mediated responses in protection after immunization with influenza vaccine. Independently living healthy elderly (>200/year; mean age 78.8-80.6/year) were recruited yearly in this four year study. The results clearly demonstrate: (1) both young and elderly consistently produced significant antibody and T cell proliferative responses to influenza vaccine upon yearly immunization; however, both responses of elderly were significantly and consistently lower than young. (2) Percentages of both young and elderly demonstrating protective titers (i.e. HI>/=40) increased post-immunization each year, but were consistently higher in young compared to elderly. (3) The risk of developing influenza disease after immunization was highest among elderly demonstrating neither antibody nor cell-mediated responses. Importantly, the risk of influenza disease was comparable in elderly demonstrating a cell-mediated response alone, an antibody response alone, or both cell-mediated and antibody responses. This suggests that cell-mediated responses play a significant role in protection in at least a subset of elderly from influenza disease after immunization.