Influenza virus-specific cytotoxic T lymphocyte (CTLs) can be obtained from mice and humans infected with influenza A viruses^1,2 and appear to be beneficial in the host response³. The viral target structure recognized by influenza virus-specific CTLs remains a controversial question for two reasons: first, previous specificity analyses were difficult to interpret because of heterogeneous CTL populations, and second, more than one viral protein has been detected serologically on the surface of influenza-infected cells^4–10. To avoid these problems, anti-influenza A/PR/8/34 CTL clones were generated and tested for cytolytic activity on target cells infected with recombinant viruses containing known rearrangements of the genes of strains A/PR/8/34 and A/HK/1/68. We report here that one such CTL line lysed target cells only if the infecting virus possessed the polymerase gene P3 of A/PR/8/34. This suggests that the P3 gene product either induces a virus-specific cell-surface antigenic modification or is expressed on the surface of the infected cell, and hence is involved in recognition of target cells by the anti-influenza CTL line.