The strength of the lymphocytic choriomeningitis virus (LCMV) model rests on the following five foundations. First, the virus in vivo in its natural host, the mouse, or in vitro in cultured cells is non-cytolytic. This quality allows clear separation of effects caused by the virus from those caused by the host immune system. Consequently, the host cell control of viral infection as opposed to how virus interacts with cells to distort their functions without killing them can be decoded. Second, reactions to LCMV infection can encompass a widely diverse range of immune responses (Fig. 1). Usually when immunocompetent adult mice are injected with LCMV, they generate a marked immune response to eliminate the infectious agent. Although their innate responses include the production of interferon (IFN), macrophages and natural killer (NK) cells (Muller et al. 1994; see reviews Buchmeier et al. 1980; Borrow and Oldstone 1997; see chapter by Biron et al., this volume), it is the adoptive immune response — primarily the virus-specific CD8⁺ CTL response — that is responsible for virus clearance.