The spontaneous mutation to drug-resistance in bacteria has been reported by many investigators (Luria and Delbruck⁽¹⁾, 1943; Oakberg and Luria⁽²⁾, 1947; Witkin⁽³⁾, 1947; Vennesland, et al.⁽⁴⁾ 1947; Yegian, et al.⁽⁵⁾, 1948; Demerec^(6,7), 1948, 1951; Newcombe, et al.^(8,9), 1949, 1951; Hsie, et al.⁽¹⁰⁾, 1950; Szybalski, et al.⁽¹¹⁾, 1953, and others) and reviewed by Luria⁽¹²⁾ (1947), Catcheside⁽¹³⁾ (1949), Braun⁽¹⁴⁾ (1953) and others. Mutation rates to drug-resistance were described by Oakberg and Luria⁽²⁾ (1947), Newcombe, et al.^(8,9), (1949, 1951), Hsie. et al.⁽¹⁰⁾ (1950), Demerec⁽⁷⁾ (1951), Szybalski, et al.⁽¹¹⁾ (1953), etc. Demerec⁽⁷⁾ (1951) estimated mutation rate to streptomycin-resistance in strain B of Escherichia coli and strain B/r, that is, a mutant of strain B resistant to radiation, and reported that the mutation rate was not appreciably affected by the strain used in tests. Szybalski and Bryson⁽¹¹⁾ (1953) estimated mutation rate to isoniazid-resistance and that to PAS-resistance in B. megaterium.

Concerning with Mycobacterium, naturally resistant forms of Mycobacterium tuberculosis have been isolated by Pyle⁽¹⁵⁾ (1947) directly from the sputa of patients who have not been treated with streptomycin, and the presence of naturally resistant mutants in stock cultures of H37Rv has been demonstrated by Vennesland, Ebert and Bloch⁽⁴⁾ (1947). A quantitative analysis of the resistance of Mycobacteria to streptomycin has been at first made by Yegian and Vanderlinde⁽⁵⁾ (1948), and the mutation rate to streptomycin-resistance has been reported by Hsie and Bryson⁽¹⁰⁾ (1950) only in Mycobacterium ranae.

However, it has been unknown whether the mutation rate of a drug-resistant mutant is the same as its parent strain or not. The present study is, therefore, concerning the mutation rate to streptomycin-resistance in a parent sensitive strain and its isoniazid-resistant mutant of Mycobacterium avium.