From 1978 to 2003, in Huntington, WV, we investigated Streptococcus pneumoniae invasive disease and the effect of conjugated pneumococcal vaccine among 161 children 14 years of age and younger admitted to the hospital. During 2002 and 2003, the number and proportion of invasive disease caused by vaccine strains declined; and in 2003, no invasive disease occurred in young children, suggesting a vaccine effect.