SUMMARY: Strains of mice differ greatly in their susceptibility to mousepox. The highly resistant strain C57 Bl has been compared with a susceptible strain of mice with regard to virus growth and antibody production.Differences in virus growth in the two strains of mice appeared at a certain stage of the infection, which was the time at which neutralizing antibody was demonstrable in the blood of resistant mice. Neutralizing antibodies, active immunity and hypersensitivity were shown to appear at least a day earlier in the resistant than in the susceptible mice.The highest degree of resistance was found in young adult C57 Bl mice (2–3 months). Resistance was very low in new‐born mice and very old mice (8–12), although death times were still delayed compared with those of susceptible mice of the same ages.The resistance of C57 Bl mice to the lethal effects of infection with ectromelia virus appears to be due to a more effective immune response than that shown by mice of susceptible strains.