Mycobacterium avium complex strain LR25, which carries 3 plasmids, was shown to be of high virulence in beige mice as judged by high mortality and a progressive increase in organisms in the spleen and lungs determined by counting the number of colony-forming units. Strain LR163, a "cured" derivative of LR25 that lacks all 3 plasmids, was of low virulence as judged by these criteria. The relative virulence of the strains was confirmed by studies of oxygen metabolite (superoxide anion and hydrogen peroxide) release from resident and BCG-activated mouse peritoneal macrophages. In contrast to loss of virulence, no significant change was seen in drug susceptibility.