Of the 90 pneumococcal serotypes, the 7 in the licensed pneumococcal conjugate vaccine (Prevnar) currently account for >80% of invasive pneumococcal infections among children in the United States. Our objective was to document and explain the changes in pneumococcal serogroup distribution in the United States during the last century. We evaluated temporal trends in the serogroup distribution, using linear regression. Between 1928 and 1998, the proportion of pneumococcal infections caused by the 7 serogroups in the conjugate vaccine increased significantly, from 15% to 59%, in 13 adult studies, and from 53% to 87%, in 19 pediatric studies. The proportion of infections caused by the "epidemic" serogroups (1-3 and 5) decreased significantly, from 71% to 7%, in the adult studies, and from 18% to 2%, in the studies of children. These historical trends in serogroup distribution may be explained by changes in antibiotic use, socioeconomic conditions, the immunocompromised status of populations, and blood-culturing practices.