Among mycobacteria, those belonging to the Mycobacterium avium complex (MAC) are the most common cause of bacteremia in AIDS patients. To understand better the mechanisms by which human macrophages kill intracellular MAC, we studied in an in vitro test system transparent morphotypes of the three most common bacteremic serotypes from AIDS patients and an opaque variant, obtained in vitro from the most mouse-virulent strain (MAC 101). The three serotypes differed in susceptibility to oxidative bactericidal mechanisms of macrophages. The transparent morphotype of strain 101 (serotype 1) was completely resistant to the intracellular killing effects of a phagocyte's reactive oxygen radicals and hydrogen peroxide, whereas strains 109 (serotype 4), 100 (serotype 8), and the opaque variant from strain 101 were killed by oxidative bactericidal mechanisms. However, even for these bacteria, non-oxidative mechanisms appear to have a role in intracellular killing.