Various phenotypes of the resistance to aminoglycoside-and peptideantibiotics of Mycobacterium tuberculosis strain H37Rv were produced by single-and/ or two-step selection of the parent strain. Mutants obtained by single-step selection with antibiotics were classified into ten phenotypes; one of single resistance, two of triple resistance, three of quadruple resistance, and four of sextuple resistance. There were two kinds of sextuple resistance (high resistance to enviomycin, viomycin, capreomycin, kanamycin, lividomycin, and paromomycin). One was isolated from the parent strain by single-step selection and could be eliminated by mutation to isoniazid resistance, the other was obtained by two-step selections and was not eliminated by mutation to isoniazid resistance. Interaction between mutation to streptomycin resistance and mutation to quadruple resistance (4R phenotype) was observed. Streptomycin resistance interfered with the formation of the 4R phenotype and produced a different phenotype, KR instead of the 4R phenotype. The existence of mutation of the 4R phenotype did not usually interfere with mutation to streptomycin resistance, but a small portion of the mutants with the 4R phenotype were altered in their phenotype from 4R to KR after addition of the mutation to streptomycin resistance. This effect of the mutation to streptomycin resistance was not observed in mutants which already had a mutation to klR phenotype (mutation to low concentrations of kanamycin only).Infection due to Mycobacterium tuberculosis is the most important subject of chemotherapy with aminoglycoside-and peptide-antibiotics. Nevertheless, studies of the system of resistance to these antibiotics, in which M. tuberculosis was used as the test strain, are very scanty. Previously, Tsukamura and Mizuno (7) reported that multiply (triply, quadruply, and sextuply) resistant mutants of M. tuberculosis strain H37Rv could be isolated by single-step selection with an antibiotic, and that the occurrence of the mutants could be the origin of the cross-resistance phenomena . Later, it was observed that the sextuple resistance was eliminated by mutation to isoniazid resistance or by incubation at high temperatures, whereas the quadruple resistance was not eliminated by these treatments (6). The present study provides further information on the resistance system of this organism : the effect of double mutations, interaction between mutation to streptomycin resistance and mutation 777