Although invasive pneumococcal infections are common among men infected with human immunodeficiency virus (HIV), the prevalence of pharyngeal colonization with Streptococcus pneumoniae was not significantly different among HIV-infected patients (8 [14%] of 56) and HIV-seronegative men (9 [9%] of 99) attending a sexually transmitted disease clinic. Sixteen HIV-infected men (mean CD4+ T cell count, 132 +/- 37/microL) developed pneumococcal bacteremia, accounting for 13.6% of 117 total cases and 42% of 38 cases in men 16-55 years old. Serum killing activity, a measure of functional humoral response to S. pneumoniae, was lower in 4 (67%) of 6 acute sera and 6 (54%) of 11 convalescent sera from bacteremic HIV-infected patients when compared with baseline sera of 7 HIV-seronegative healthy subjects. These findings suggest that the high rates of pneumococcal bacteremia among HIV-infected patients may be associated with low numbers of CD4+ T cells and impaired humoral responses to S. pneumoniae rather than to increased exposure to the organism.