The current tuberculosis vaccine, BCG, has questionable efficacy and undoubtedly new vaccines are needed. Recent studies have indicated that DNA vaccines may be promising as new mycobacterial vaccines candidates. We have generated DNA vaccines expressing 10 different mycobacterial agents. Five of these vaccines have been tested in animal models. We have shown the DNA vaccines expressing ESAT6, katG, HBHA, and Antigen 85 induce a humoral response in muc and increase levels of interferon-gamma. Studies are in progress to evaluate whether these DNA vaccines, administered either singly or in combination, can protect mice against tuberculosis challenge.