DNA vaccines can induce cytotoxic T lymphocyte (CTL) responses in various species including mice, non-human primates and humans. It is now well established that antigen presenting cells (APCs) are required for induction of these responses. However, it is not yet known whether this is a function of antigen expression within or acquisition of antigen by these cells, or a combination of both. Cross-priming has been demonstrated to occur from cells (including muscle cells) to APCs in vivo. In addition, there is evidence that APCs can be transfected after DNA vaccination. Hence, efforts to facilitate cross-priming and to increase transfection of APCs will be important for increasing the potency of DNA vaccines.