SUMMARYWe analysed the production of interferons (IFN)-alpha and -gamma during the generation of human influenza-virus specific cytotoxic T lymphocyte (CTL) responses using monoclonal antibodies in a specific radioimmunoassay. The results showed that the peripheral blood mononuclear cells (PBM) of all donors tested produced IFNgamma and had influenza A virus-specific CTL activity after stimulation. The amount of IFN-gamma produced and the level of CTL activity were significantly correlated. The PBM of some donors also produced IFN-alpha. The level of IFN-gamma produced was low during the first few days and increased subsequently, but IFN-alpha, when it was detected, was produced on day 1. The kinetics of the increase in IFNgamma correlated with the increase in CTL activity. We also observed an increased percentage of cells bearing interleukin-2 receptors, which may have been a response to the production of IFN-gamma. The T cells active in lysing influenza A virus-infected target cells and in producing IFN-gamma were determined after separating effector cells with monoclonal antibodies. The CTL effector cells were mainly in the T8 ÷ subset, but IFN-gamma-producing cells were found in both T4 ÷ and T8 + subsets. These results suggest that influenza virus-specific T8 ÷ CTL produce IFN-gamma in response to virus, and that T4 + cells which are not CTL effectors also produce IFN-gamma after restimulation with influenza A virus-infected cells.