Immunological adjuvants help increase the number of T cells responding to an immunizing antigen. Part of the increase is due to promotion of survival of clonally expanded T cells in the face of waning antigen load and subsequent growth-factor withdrawal. The phosphatidylinositide-3 kinase (PI3-kinase)/Akt pathway is activated upon T cell stimulation and plays a critical role in clonal expansion by mediating several aspects of co-stimulation in a growth-factor-dependent manner. We hypothesized that adjuvants must either cause the PI3-kinase/Akt pathway to operate in the absence of growth-factor or to render T cells independent of continuous PI3-kinase signaling for their survival. To determine which is true, mice were treated with model antigen in the presence or absence of the natural adjuvant lipopolysaccharide (LPS). T cells from treated mice were assayed for their dependence on PI3-kinase signaling by measuring (i) levels of phosphorylated Akt, (ii) survival after culture in the presence of the PI3-kinase inhibitor LY294002, and (iii) the amount of glucose uptake upon ex vivo culture. The results show that although LPS treatment increased the induced PI3-kinase activity, the presence of PI3-kinase inhibitor did not affect glucose uptake or survival of T cells, an attribute the cells acquired within 4 h of LPS injection. Therefore, adjuvant-dependent survival effects do not require continuous PI3-kinase activity to occur, a finding that may explain how activated T cells survive antigen-withdrawal long enough to traffic from priming lymph nodes to sites of infection.