Active, laboratory-based surveillance for cases of invasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from a normally sterile site, was conducted through Active Bacterial Core surveillance of the Emerging Infections Program network (8). We included cases diagnosed between 1 January 1998 and 31 December 2003 among surveillance-area residents who were 18 to 64 years of age. We limited the analyses to 7 surveillance sites, including California (San Francisco County), Connecticut (entire state), Georgia (8-county Atlanta metropolitan area), Maryland (City of Baltimore and 5 neighboring counties), Minnesota (7-county Minneapolis–St. Paul metropolitan area), Oregon (3-county Portland metropolitan area), and Tennessee (Davidson, Hamilton, Knox, Shelby, and Williamson Counties). Information was systematically collected on the HIV status of case-patients at these sites. In 2003, the resident adult population in these 7 areas was 10.8 million (4.5% of the U.S. population between 18 and 64 years of age) (9) and included 9.5% of the estimated number of adults living with AIDS in the United States (10).