Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex (MAC) organisms cause bacteremia in patients withAIDS. Cultured human-monocyte-derived macrophages and murine Kupffer cells were exposed to 10–100 µg/dl ethanol; significantly greater intracellular growth of MAC strains1 00 (serovar 8) and 101 (serovar 1)occurred in ethanol-treated cells than in controls (range, 58% ± 7%–70% ± 5%; P < .05 for 50 and 100 µg/dl ethanol vs. control). Both cell types, when treated with 103 units/ml recombinant tumor necrosis factor (TNF) or 102 units/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence of 10–100 I-tg/dl ethanol,killed significantly fewer MAC than controls (49% ± 12% decrease for GM-CSF and 57% ± 16% for TNF; P < .05 for all comparisons). C57BL black mice infected intravenously with MAC strain 101 were given ethanol as 4% of total calories daily; after 21 days they had greater numbers of MAC in blood, liver, and spleen than controls. Ethanol's effects on the interaction between theh ost and MAC favor progressive infection.