The incidence of bacteremia and meningitis due to Streptococcus pneumoniae is highest among preschool-age children, particularly those < 2 years of age. Clinical trials of capsular polysaccharide vaccines among young children have been disappointing. Conjugation of bacterial polysaccharides to proteins can increase antibody responses following vaccination of young children. Most conjugate vaccines proposed to date have been seven-valent. To identify serotypes most commonly associated with infection in young children, we serotyped pneumococcal isolates submitted to the CDC through national surveillance from 3884 children < 6 years old with pneumococcal bacteremia (n = 3169), meningitis (n = 401), or otitis media (n = 314) from 1978 to 1994. Seven serotypes (14, 6B, 19F, 18C, 23F, 4, and 9V) accounted for 3045 (78%) isolates. A conjugate pneumococcal vaccine protecting against these seven serotypes and serologically cross-reactive serotypes could potentially prevent 86% of bacteremia, 83% of meningitis, and 65% of otitis media cases. The proportion of isolates covered by such a vaccine increased from 78% to 87% from 1978 to 1994. Of 70 isolates submitted during 1992-1994 which were nonsusceptible to penicillin (minimal inhibitory concentration [MIC] > 0.1 microgram/mL, 56 (80%) were among the seven most prevalent serotypes. All 21 isolates resistant to penicillin (MIC > or = 2.0 micrograms/mL) were among these seven serotypes.