Unlike typical naive T cells, T cells with an activated (CD44hi) memory phenotype show a rapid rate of proliferation in vivo . The turnover of memory–phenotype CD8+ T cells can be considerably augmented by injecting mice with various compounds, including polyinosinic–polycytidylic acid, lipopolysaccharide and immunostimulatory DNA (CpG DNA). Certain cytokines, notably type I (α, β) interferons (IFNI), have a similar effect. These agents appear to induce proliferation of CD44hi CD8+ cells in vivo by an indirect process involving production of effector cytokines, possibly interleukin–15, by antigen–presenting cells. Although none of the agents tested induces proliferation of naive–phenotype T cells, IFN–I has the capacity to cause upregulation of surface markers on purified naive T cells. Depending upon the experimental conditions used, IFN–I can either inhibit or enhance primary responses of naive T cells to specific antigen.