Lungs of H-2k mice co-inoculated with type A/WSN influenza virus+detective interfering WSN virus contain haemagglutinin (HA)-specific IgG which have three different activities. These have been purified by adsorbtion and elution using different forms of HA. The first IgG recognizes HA in a form present on H-2k cells infected with a vaccinia virus recombinant expressing the WSN HA gene (vaccinia-HA virus), but not on virus particles, and enhances class I major histocompatibility complex (MHC)-restricted killing of WSN-infected H-2k target cells by primary cytotoxic T lymphocytes (CTL) from the lungs of WSN-infected H-2k mice; it also confers on primary CTL from the lungs of WSN-infected H-2d mice the ability to lyse WSN-infected H-2k targets. This IgG is therefore analogous to the T-cell receptor in that it is antigen specific and MHC restricted. A second IgG recognizes HA in a form present on both H-2k and H-2d cells infected with the vaccinia-HA virus but not present on virus particles and inhibits CTL lysis of WSN-infected syngeneic target cells. Only the third binds to virus particles; this inhibits agglutination of red cells, but is non-neutralizing. It also inhibits CTL lysis of WSN-infected syngeneic targets. Thus we present evidence that HA-specific IgG may have a significant role in regulating CTL responses to influenza virus in vivo and that one of these IgG is MHC-restricted in its recognition of viral antigen. Finally, in vivo significance of these antibodies is indicated by the finding that adoptively transferred CTL-enhancing IgG protects mice from lethal WSN infection.