Streptococcus pneumoniae is a major cause of pneumonia, bacteremia, and meningitis, especially among adults infected with the human immunodeficiency virus (HIV). Alveolar macrophages (AMs) are critical components of cellular defense against bacterial infection and are both infected and affected by HIV. In this study, AMs obtained at bronchoscopy from 44 Malawian adults (24 HIV positive and 20 HIV negative) were exposed in vitro to opsonized S. pneumoniae and coagulase-negative staphylococci. AMs from HIV-positive and -negative volunteers showed no significant difference in binding to or internalization of either S. pneumoniae or coagulase-negative staphylococci. In HIV-positive subjects, the presence of detectable HIV in lung fluid was not associated with AM impairment. AMs from HIV-infected adults did not exhibit impaired pneumococcal phagocytosis in the assay used. This suggests that an alternative mechanism of susceptibility is operating in these individuals.