Information on the pathogenesis of Mycobacterium intracellulare disease is necessary to facilitate the finding of effective drugs. As a first step, development of a suitable smallanimal model is needed. Examination of several strains of mice and M. intracellulare led us to conclude that the Swiss Webster strain of mice and the 8330 and 571-8 strains of M. intracellulare were most useful. Since the use of normal mice resulted only in a chronic type of disease lasting many months, immune suppression by means of trypan blue, silica, or a combination of cyclophosphamide and cortisol was attempted in order to generate an acute infection. Higher numbers of bacilli were recovered from organs in the immune-suppressed animals as compared with the controls, more so in the lungs than in the spleen, although no acute type of disease process resulted.