The effect of levamisole (1-2,3,5,6-tetrahydro-6-imidazo[2,1-b]thiazole monohydrochloride) treatment on the course of a Corynebacterium pseudotuberculosis infection and the ability of either vaccinated or unvaccinated randomly bred mice to resist challenge were investigated. It was found that either a double treatment of levamisole administered with or without a sublethal inoculation of C. pseudotuberculosis or a single treatment of levamisole alone had a significant effect on the ability of mice to resist challenge with virulent C. pseudotuberculosis. This prolonged, enhanced nonspecific and specific resistance was associated with a quantitative reduction in the geometric mean serum immunoglobulin levels, with the immunoglobulin G2 and immunoglobulin A levels being more severely affected. As the enhanced nonspecific resistance to C. pseudotuberculosis was associated with depressed serum immunoglobulin levels in the mice pretreated with levamisole alone, it was suggested that the cell-mediated immunity may play a more important role than the humoral immunity in the resistance to C. pseudotuberculosis infection.