[Purpose] In this study, we examined the fluctuation in the ratio between strains of tuberculosis bacilli resistant and susceptible to the anti-tuberculosis drugs.[Material & method] We selected the cases in which the bacilli acquired drug resistance during the therapy and the cases in which drug resistance was fluctuating during pro-longed anti-tuberculosis treatment. We selected the isolates throughout the medication period, and the selected isolates were separated into respective single colonies. Then we mea-sured the minimal inhibitory concentration (MIC) for each colony by microdilution test for M. tuberculosis complex, BrothMIC MTB-1 (Kyokuto Pharmaceutical Inc., Tokyo).[Results] Five patients were eligible for analysis because their medical histories were clearly recorded and drug resis-tance changed during the course. The MIC of 19 isolates, 202 colonies were measured. Isolates with coexisting drug-resis-tant and -susceptible colonies were detected in 2 patients. From these results, we considered that the fluctuation in the ratio between drug-resistant and -susceptible bacilli changes with the progression of anti-tuberculosis medication.[Conclusion] We showed in this article that the drug-resis-tant bacilli increased rapidly when the strains acquired the drug resistance during medication, and when the administration of particular anti-tuberculosis drug was stopped, the sus-ceptible bacilli seemed to increase gradually. However, the strain immediately became fully drug-resistant when the particular antibacterial drug was readministered.