HIV-infected individuals frequently develop Mycobacterium tuberculosis (MTB) infection. Alveolar macrophages are the initial host defense against this organism. We measured MTB growth in alveolar macrophages from normal and HIV-infected subjects after in vitro exposure. Intracellular growth of MTB was reduced in alveolar macrophages from HIV-infected subjects compared to normal macrophages. This was confined to subjects with CD4 counts greater than 200/ul. Growth of avirulent mycobacteria in HIV macropahges was significantly less than virulent MTB. Since avirulent MTB is more sensitive to tumor necrosis factor-, we examined the relationship between cytokine secretion and mycobacterial growth. Higher alveolar macrophage spontaneous tumor necrosis factor- secretion was associated with reduced MTB growth in normal alveolar macrophages. This relationship was not seen in HIV-infected subjects, suggesting other factors contributed to mycobacteria resistance. Mycobacteria-induced tumor necrosis factor- secretion was inversely associated with growth in normal alveolar macrophages but not in HIV-infected subjects. Finally, binding and internalization of MTB was augmented in HIV macrophages compared to normal, demonstrating that reduced intracellular MTB growth was not due to impaired phagocytosis. In conclusion, the increased incidence of MTB infection in HIV-infected subjects does not appear to be due to a defect in macrophage innate immunity.