A scientific review of bovine tuberculosis in Great Britain has concluded that the development of a cattle vaccine holds the best prospect for long-term disease control. Recent reports of successful DNA vaccination against Mycobacterium tuberculosis in small animal models have raised the possibility of using a similar strategy to produce vaccines against Mycobacterium bovis infection in cattle. To test this possibility, BALB/c mice were immunized with DNA encoding the M. bovis antigen MPB83. The mice responded to vaccination with a mixed IgG1/IgG2a response to the antigen and were protected from intravenous challenge with virulent M. bovis to a similar extent as those vaccinated with bacille Calmette-Guérin. The immunogenicity of the DNA vaccine in cattle was tested, after having established that DNA encoding MPB83 was immunogenic and elicited protective immunity in mice. In these studies, vaccinated animals had strong proliferative responses to MPB83.