An influenza A subtype cross-reactive CTL clone (A-11) was established following stimulation of A/PR/8 virus-immune spleen cells of Balb/C (H-2d) mice. This T cell clone lysed target cells infected with influenza viruses of the H1, H2, or H3 subtypes, and recognizes a conserved epitope on the NS1 protein. The clone is restricted by the H-2Ld allele. Adoptive transfer of A-11 significantly reduced virus titers in the lungs of mice infected with influenza A viruses of the H1, H2, or H3 subtypes. These results suggest that the conserved epitope on NS1 which is recognized by A-11 may be a useful component to consider for inclusion in experimental cross-reactive influenza vaccines.