Adoptive transfer of TCR‐transgenic T cells uniformly expressing an identifiable TCR of known peptide/MHC specificity can be used to monitor the in vivo behavior of antigen‐specific T cells. We have used this system to show that naive T cells are initially activated within the T‐cell zones of secondary lymphoid tissue to prohferate in a B7‐dependent manner. If adjuvants or inflammatory cytokines are present during this period, enhanced numbers of T cells accumulate, migrate into B‐cell‐rich follicles, and acquire the capacity to produce IFN‐7 and help B cells produce IgG2a. If inflammation is absent, most of the initially activated antigen‐specific T cells disappear without entering the follicles and the survivors are poor producers of IL‐2 and IFN‐γ Our results indicate that inflammatory mediators play a key role in regulating the anatomic location, clonal expansion, survival and lymphokine production potential of antigen‐stimulated T cells in vivo.