Influenza A virus-specific MHC class I-restricted cytotoxic T lymphocyte (CTL) activities among young and elderly adults were compared. Peripheral blood lymphocytes from 10 young adults, (mean age 27 ± 2.4 years) and elderly persons (mean age 71 ± 1.6 years) were stimulated with influenza A/Taiwan/1/86 (H1N1) virus for 7 days and assayed for lytic activity against A/Taiwan, A/Shanghai (H3N2), and B/USSR virus-infected autologous target cells. Young adults exhibited significantly higher influenza A cross-reactive CTL activity against A/H1N1 and A/H3N2 target cells when compared to aged persons. This was true at all effector-to-target cell ratios tested. Negligible lysis of B/USSR-infected target cells or nonautologous A/Taiwan-infected cells was observed. The number of leukocytes recovered per milliliter of blood was also significantly higher in young adults than in old donors; however, the percentage of CD45⁺ (common leukocyte antigen), CD3⁺ (T cells), CD4⁺ (T helper), and CD8⁺ (T cytotoxic/suppressor) as well as the CD4⁺/CD8⁺ ratios was similar in both groups. Depletion of cells with monoclonal antibodies indicated that the effector cells were CD8⁺ T cells. Serum-neutralizing antibody (Nt Ab) titers were similar among young and elderly persons and there was no correlation between Nt Ab and CTL activity. These results demonstrate a reduced influenza virus-specific MHC class I-restricted CTL activity among elderly persons. The deficiency in this cell-mediated immune function may contribute to the morbidity and mortality from influenza virus infections in this population.