Groups of C57BL/6J, BALB/c, BALB/c, nu+/nu+ mice, inoculated intranasally with Corynebacterium parvum (350 micrograms/mouse) were protected from death by an otherwise lethal dose of influenza virus, A/WSN (H1N1) inoculated 3 days later. The lungs of C. parvum-treated, virus-infected C57BL/6J, BALB/c, or BALB/c nu+/nu+ mice contained significantly less infectious virus than did controls, and this reduction was apparent as soon as 24 hr after virus inoculation. The maximum protective effect correlated with increased lung interferon levels. C. parvum treatment caused an increase in the lung cell number which was in part due to a large increase (ca. 10-fold) in macrophage content, and the natural killer cell activity was also enhanced, though not as markedly as occurred 3 days after infection. Most (greater than 85%) of the resident macrophages in normal lungs were susceptible to infection by virus (as indicated by hemadsorption), whereas most of those recovered from the lungs of C. parvum-treated mice resisted infection. Despite the increase in macrophage content, the level of specific immune responses to infection, such as cytotoxic T-cell activity, DTH reaction, and antihemagglutinin antibody, remained unchanged by C. parvum treatment so that the major if not only effect of this treatment was on the level of the less-specific components of the immune system.