Mycobacterium avium complex (MAC) organisms are the most common bacterial cause of disseminated infection in patients with AIDS. MAC, facultative intracellular bacteria, invade and multiply within macrophages. Treatment of MAC-infected macrophages with ethanol (10-100 micrograms/dL) is associated with increased intracellular multiplication of MAC. To investigate whether this enhanced growth is due to a stress-related response induced by nonlethal concentrations of ethanol, strain 101 (serovar 1) was exposed to ethanol, and the regulation of the expression of proteins was examined. Exposure of MAC to ethanol (range, 10-100 micrograms/dL) was associated with up-regulation of the expression of a number of bacterial proteins, some of which (65 and 33 kDa) interfered with macrophage functions, such as production of superoxide anion and killing of Staphylococcus aureus. Thus, exposure of MAC to small concentrations of ethanol may induce a stress-related response with consequent increase in the synthesis of proteins possibly associated with its ability to survive within macrophages.