Adherence of Mycobacterium lepraemurium to tissue culture cells was examined and compared with that of M. microti. M. lepraemurium used in the present study was maintained on 1% Ogawa egg yolk medium. This microbe adhered to HEp-2 cells much more than A31 or McCoy cells, though the adherence was unusually low as compared with the large infectious dose. Frequency distribution of the number of bacteria agreed nearly with Polya-Eggenberger distribution. The pretreatment of M lepraemurium with heat or protease increased the adherence of the bacteria to HEp-2 cells, whereas the pretreatment with lipase or hyaluronidase retained the adhering ability. The pretreatment of M. microti with heat or protease produced the same effect on the adherence as that of M. lepraemurium. These results suggest that adherence of M. lepraemurium to HEp-2 cells is prevented by protein-like material on the surface of the bacteria, and that the adherence is independent of specific adhesin-receptor interaction.