Natural killer (NK) cells are recruited locally during the initial phases of virus infection and produce cytokines which may affect the subsequent emergence of specific T cells. In this study, cellular responses to primary respiratory syncytial virus (RSV) infection and after vaccination with individual viral proteins were investigated in BALB/c mice using the new NK cell antibody, DX5. Purified DX5 cells caused lysis of YAC-1 cell targets. DX5 cells did not express CD8, CD45R or MHC class II antigens. A small proportion of DX5 cells coexpressed CD4 (10·3%) and CD3 (10·6%). Of the DX5 /CD4 cells, the majority expressed the α/β T cell receptor and less than 1 % expressed the γ/δ T cell receptor. During infection with RSV, lung DX5 /CD3 NK cells peaked on day 4 of primary infection and were the most numerous subset producing IFN-γ, as determined by intracellular staining, at this time-point. Less than 1% of the DX5 cells secreting IFN-γ were CD4 . In the lungs of mice vaccinated with recombinant vaccinia virus expressing individual RSV proteins, increased NK cell cytotoxicity and IFN-γ production correlated with increased numbers of CD8 T cells. Mice with few NK cells subsequently had low CD8 T cells and developed lung eosinophilia. IFN-γ-producing NK cells therefore form a substantial component of the early cellular response to virus infection with important potential influences on the subsequent development of specific immunity.