Human immunodeficiency virus (HIV) is an important risk factor for invasive pneumococcal disease, but information on clinical course and infecting serotypes is limited. To help develop strategies to reduce the morbidity due to invasive pneumococcal disease, episodes ofpneumococcal bacteremia were identified by retrospective review of microbiology records (November 1983–November 1987) at 10 San Francisco hospitals and, for patients 20–55 years old living in San Francisco, HIV antibody status was determined by review ofmedical records. Pneumococcal isolates from one hospital were serotyped. Of 294 patients with pneumococcal bacteremia identified, 32 (11%) had AIDS at the time pneumococcal bacteremia was diagnosed and another 43 (15%) were HIV–infected but did not have AIDS; 12 HIV–infected patients developed AIDS after the episode of pneumococcal bacteremia. The rate of pneumococcal bacteremia in AIDS patients was estimated to be 9.4/1000 patient–years. Serotypes of 27 (82%) of 33 pneumococcal isolates from HIV–infected patients and 107 (90%) from 119 patients without known HIV infection were among the 23 serotypes included in the currently available polysaccharide vaccine. The rate of pneumococcal bacteremia is ˜100-fold greater in AIDS patients in San Francisco than rates reported before the AIDS epidemic, but more than halfthe episodes ofpneumococcal bacteremia in HIV–infected patients occurred in patients without AIDS. Data on pneumococcal serotypes causing invasive disease in HIV–infected patients suggest that the current pneumococcal vaccine, if effective in this population, could provide significant protection against pneumococcal disease.