The ability of Mycobacterium lepraemurium (Mlm) to adhere to A31 cells in culture decreased with the number of passages of the bacilli on Ogawa egg-yolk medium. Pathogenic Mlm consistently grew in tissue culture cells but growth was not seen with attenuated Mlm isolated from a smooth colony. After prolonged incubation, attenuated Mlm became adapted to tissue culture growth. The pathogenicity of the attenuated bacilli was restored partially by the adaptation to tissue culture cells and restored almost completely by passage in mice. After restoration of pathogenicity by these methods, the Mlm formed rough-type colonies on Ogawa egg-yolk medium although the colonies were not completely of the rough type. Attenuated Mlm did not interfere with the growth of in vivo-derived Mlm in tissue culture or in mice.