Mice of the inbred strains C57/BL and C3H were inoculated subcutaneously on the thorax withM. lepraemurium.In C57/BL mice a firm, raised, sharply defined nodular infiltrate developed 4 weeks afterwards, while in the C3H strain the infection produced a soft, flattened infiltrate with ill‐defined margins, which did not become palpable until 10 weeks after inoculation. A limited spread of the infection occurred early in both strains, but apparently multiplication of the microorganisms was very restricted in C57/BL mice; progressive, disseminated growth of the bacilli was observed in the C3H strain only. In C57/BL mice the granulomatous reaction, developing 4 weeks after inoculation and leading to abcess formation, ulceration and scar formation, apparently inhibited both local multiplication and further spread of the bacilli. In C3H mice no host reaction was detected and the bacilli appeared to grow unrestrictedly. In some C57/BL animals, decrease in host resistance occurred during the infection, causing reactivation of the local lesion and an apparently rapid proliferation of bacilli. Observations regarding the lesions in superinfected animals indicated that a systemic immune reaction develops in the C57/BL strain about 4 weeks after inoculation, whereas this does not occur in the C3H strai