Different vaccination procedures to increase the mechanisms of host resistance to Nocardia brasiliensis were studied in mice. When mice were challenged in the footpad, 2 x 10(8) N. brasiliensis 20 days after footpad inoculation with either viable or killed N. brasiliensis, the mice demonstrated significant resistance to infection when compared with noninfected and nonimmunized mice. The degree of resistance seems to be correlated with the delayed-type hypersensitivity response in the vaccinated animals. Vaccination with another acid-fast bacilli, BCG, afforded both a mild protection and low DTH reactivity. Antibody levels to Nocardia were similar in either Nocardia- or BCG-treated groups indicating that they do not play an important role in resistance to infection by N. brasiliensis.