The functional capacities and surface phenotype of the cells that accumulate in the lungs of hamsters during influenza A virus (PR/8/34) infection were studied to determine the cellular mechanisms that may limit the viral infection in the lung. Nonspecific natural killer (NK) cytotoxicity was augmented early (3 days) after infection in the lung but was undetectable at 6 days postinoculation. Virus-specific cytotoxic cells were detected within populations of mononuclear cells harvested from the lung but not from the hilar lymph node or spleen of influenza-infected hamsters following intratracheal inoculation. In contrast to virus-specific cytotoxic activity which remained locally, delayed-type hypersensitivity (DTH) activity was detected in assays in which cells were used from lung, hilar lymph nodes, or spleen. Depletion studies using rabbit anti-asialo GM1 and newly developed mouse monoclonals WI20 and WI38, which detect surface antigens on hamster T-lymphocyte populations, demonstrated that in the hamster NK cells are asialo GM+, WI20-, WI38-; DTH lymphocytes are asialo GM-, WI20+, WI38-; and cytotoxic T lymphocytes are asialo GM-, WI20+, WI38+. Together these data suggest that antigen-specific cytotoxic T cells can be induced locally within the hamster lung during influenza infection, but that they appear to be unable to circulate systemically, unlike the T cells that mediate DTH. Thus while the lung appears to share some immune responses to local infections with peripheral lymphoid organs, effector cells can be induced to develop locally and may be regulated locally without a mandatory involvement of the systemic immune system.