THE molecular basis of recognition and target cell killing by cytotoxic T cells is still unknown. Doherty and Zinkernagel showed that mouse cells infected with lymphocytic choriomeningitis virus can be lysed by immune cytotoxic T cells but only if both cell types share at least part of the major histocompatibility (H–2) region (see ref. 1). H–2 compatibility is also required for cell killing in other viral systems^2–4, and for cells carrying non-viral antigens^5–7. Our aim is to analyse the virus specificity of cytotoxic T cells, and the nature of their antigen recognition units. This requires a virus system with a small number of well characterised protein components, amenable to biochemical and genetic manipulation, as well as cytotoxic cells that will lyse target cells in a short term assay to minimise nonspecific cytotoxicity. Influenza virus offers many advantages for this type of study. The virion contains only two well characterised surfaced antigens, haemagglutinin (H) and neuraminidase (N), that are also expressed on the surface of infected cells^8–11, and can be purified in quantity. Virus strains are available with serologically distinct surface proteins, and with different internal proteins^12,13. Here we describe the generation of potent cytotoxic cells that are specific for histo-compatible influenza virus-infected cells, but exhibit extensive cross-reactivity between the different type A influenza virus strains.