Although Mycobacterium tuberculosis (MTB) and its purified protein derivative (PPD) induce HIV in cell lines that harbor latent HIV infection, it is not known whether similar activation of HIV in primary macrophages infected with HIV occurs. This possibility was examined using alveolar macrophages (AM) obtained by bronchoalveolar lavage of HIV-infected subjects with CD4 counts <200/microl. PPD induced transcription of HIV in AM from HIV-infected subjects by reverse transcription-polymerase chain reaction (RT-PCR). PPD and MTB infection also induced HIV production in AM from these HIV-infected patients, determined by HIV p24 enzyme-linked immunosorbent assay (ELISA). Viral production in AM required short periods of cell contact with allogeneic lymphocytes. HIV was only inducible, however, in AM from subjects with detectable HIV load (one to three copies of HIV DNA/1000 cells). Thus, MTB and its PPD can induce HIV in latently infected AM.