CD8 T-cell priming following DNA vaccination has been shown to confer protection against infections and tumors. These vaccines, however, have been disappointing in their ability to boost memory responses in prime-boost settings. We recently found that migratory dendritic cell (DC) subsets inefficiently stimulate memory CD8 T cells, raising the possibility that the poor boosting capacity of DNA encoded antigens might relate to their presentation by subsets of DCs that are only capable of efficiently stimulating naive T cells. Here, we show that DCs are required for T-cell priming in vivo following intradermal immunization with DNA-encoded antigens and that epidermal Langerhans cells are relatively unimportant. We then provide evidence that naive and memory CD8 T cells respond equally to DNA-encoded antigen. These findings show that immunization to DNA-encoded antigens is strongly DC-dependent and that the failure to boost memory T-cell immunity efficiently is not a consequence of a differential capacity of this form of antigen to stimulate naive or memory T cells.