Interferon (IFN) induced during a virus infection mediates antiviral effects both by direct inhibition of virus replication and by influencing the proliferation, differentiation, and chemotaxis of cyto‐toxic lymphocytes which control the infection. Cells from tissue taken from virus‐infected mice are conditioned by IFN to resist lysis by natural killer (NK) cells, while they become increasingly susceptible to lysis by cytotoxic Tlymphocytes (CTL). This is due to marked IFN‐induced biochemical changes, including an up‐regulation of major histocompatibility antigens, which are targets for (...) CTL. Cytopathic viruses, which inhibit cellular RNA and protein synthesis, render target cells refractory to IFN‐mediated protection against NK cells, thereby providing a mechanism for NK cells to mediate antiviral effect by preferentially lysing virus‐infected but not uninfected cells. (shrink)