The purpose of this study was to characterize systemic Streptococcus pneumoniae disease in human immunodeficiency virus type 1 (HIV-1)-infected children. All cases of bacteremia and meningitis caused by S. pneumoniae among children less than 18 years old were collected by review of the Microbiology Laboratory records at the Bellevue Hospital Center during the period August 1, 1978, through July 31, 1993. There were 31 bouts of systemic S. pneumoniae disease in 19 of 235 HIV-1-infected children cared for by the Pediatric Infectious Disease staff and 116 bouts in 113 children not known to be HIV-1-infected. Four of the 19 HIV-1-infected children had multiple episodes of S. pneumoniae bacteremia as compared with 3 of 113 in the general population (P = 0.008). The frequency of serotypes and distribution of infections by season of the year did not differ between the 2 groups. The median ages at the time of the S. pneumoniae infection were 1.8 and 1.1 years for the HIV-1-infected children and the general population of children, respectively, when those children with multiple episodes were included for their initial episode only (P = 0.06). In the HIV-1-infected patients, 10 episodes were associated with pneumonia, 5 with pneumonia and otitis media, 5 with otitis media only, 1 with pneumonia and meningitis, 1 with meningitis only and 1 with periorbital cellulitis; 5 had no apparent focus of infection. One episode of pneumonia was complicated by lung abscess and there were 2 deaths. Most HIV-1-infected patients recovered without significant sequelae, and the clinical course of their systemic infections did not appear to be markedly different than that of healthy children.