Influenza virus infection of C57BL/6 mice provides a well-characterized model for the study of acute CD8(+) T cell responses and for the analysis of memory in the absence of antigen persistence. The advent of tetramer reagents and intracellular cytokine staining, coupled with techniques such as single cell RT-PCR and influenza reverse genetics, has enabled the detailed molecular dissection of different epitope-specific primary, memory and secondary immune CD8(+) T cell responses. The approach offers novel insights into the factors determining the selection of immune repertoires, and their functional consequences for CD8(+) T cell-mediated immunity.