Experimental tuberculosis in guinea pigs infected with cultures of H(37)Rv strain exhibing high degrees of resistance to SM, PAS and INH and subsequently treated with usual dose and large dose of INH, combined administration of INH and sulfonamide compounds, SM and KM was carried out. Also a clinical observation of reversal of infectiousness of the tubercle bacilli in the sputum of the patients with chronic pulmonary tuberculosis was performed by this treatment regime. The results lead to the following conclusions. In the experimental tuberculosis, administration of the usual dose and large dose of INH and combined administration of INH and sulfonamides revealed remarkable effectiveness to the SM- and PAS-resistant strains and considerable to the INH-resistant strain. Administration of the large dose and combined treatment of INH and sulfonamides were more effective than the usual dose of INH. In clinical observation, these kinds of INH treatment showed same tendency as in the animal experiment. So it is thought that these treatment regime of INH should be tried in the treatment of the patients with INH resistant tuberculosis. However, in this experiment, administration of the further larger dose of INH did not show the more remarkable effectiveness and it may be considered that there is a limit in the effectiveness in the treatment of the large dose of INH. Administration of SM to the animals with even low degrees of SM resistant strain scarcely showed its effectiveness and it should be warned to administer SM to the patients with SM-resistant tubercle bacilli. Although KM revealed somewhat lesser effectiveness than SM of the same dose, KM brought marked effectiveness to each resistant strain and showed no cross resistance to SM-, PAS- and INH-resistant respectively. The sulfonamides revealed low antituberculovs effectiveness in the experimental tuberculosis in guinea pigs and it is thought that single administration of the sulfonamides to tuberculosis is unable to be expected thier effectiveness. But it is a point of interest that the blood level of sulfadimethoxine was showed to keep a high and long-lasting.