CpG‐containing oligodeoxynucleotides (CpG‐ODN) act as powerful adjuvant during in vivo induction of T cell responses. While CpG‐ODN directly activate antigen‐presenting cells (APC) and thus exert an extrinsic activity on T cells, it is unclear whether they directly affect T cells (intrinsic activity). Here we analyze the effects of CpG‐ODN on T cells in an APC‐free cell culture. We report that CpG‐ODN co‐stimulate T cells provided they were triggered via their TCR. CpG‐ODN induced IL‐2 production, IL‐2 receptor expression and thus proliferation. Proliferation was blocked by cyclosporin A or anti‐IL‐2 monoclonal antibodies (mAb) but not by anti‐IL‐4 mAb. Moreover, CpG‐co‐stimulated T cells differentiated into cytolytic T lymphocytes in vitro. Of note, IL‐2‐driven growth of primed T cells was not affected by CpG‐ODN. Co‐stimulation was also operative in T cells from CD28^{− / −} mice and in TCR‐transgenic T cells stimulated with peptide. CpG‐ODN‐mediated co‐stimulation of T cells in vitro may thus explain part of the potent adjuvant effects of CpG‐ODN in vivo.