Mycobacterium simiae is an environmental organism that has rarely been associated with human disease. In Israel M. simiae is frequently isolated from clinical specimens, and it usually colonizes damaged lungs. Until now, only two cases of AIDS patients with M. simiae infection have been reported, and these patients were coinfected with Mycobacterium avium complex. Two Israeli patients with AIDS complicating hemophilia developed prolonged fever that was unresponsive to therapy with broad-spectrum antibiotics. One of them had cavitary pulmonary infiltrates. M. simiae was isolated from blood in both cases and from sputum and bone marrow in one case. The identity of the mycobacterium was confirmed at three reference laboratories. Both patients died of the infection. Thus, the possibility of M. simiae infection should be considered for AIDS patients who live in areas where this mycobacterium is prevalent.