It is accepted that T cells play a critical role during virus infections; however, T cell responses in vivo in acute stage of virus infection are not understood. We examined T cell activation in vivo in two volunteers who developed dengue fever in response to vaccination with a candidate live dengue vaccine. Serial plasma collected from the volunteers from day 0 (before infection) to day 17 after infection were examined for levels of soluble interleukin-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8), interleukin-2 (IL-2) and interferon gamma (INF gamma). Elevation of the levels of sIL-2R, IFN gamma, sCD4 and IL-2 became obvious during the period of viremia and was followed by a later increase in the level of sCD8. The levels of IFN gamma and sIL-2R declined after the end of the period of viremia. These results indicate that i. T cells are activated in vivo by dengue virus infection ii. activation of CD4+ T cells occurs during the period of viremia iii. activation of CD8+ T cells follows CD4+ T cell activation. These results suggest that activation of T cells in vivo may contribute to controlling acute dengue virus infections.