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The objective was to determine whether there has been a significant decrease in the incidence of invasive Streptococcus pneumoniae disease in the Louisville, KY, area since heptavalent pneumococcal conjugate vaccine was introduced in the winter of 1999–2000. A secondary objective was to collect demographic data regarding invasive S. pneumoniae disease in the Louisville, KY, area during the 1997–2002 period.Data on cases of invasive S. pneumoniae disease (defined by a positive culture for S. pneumoniae from the blood, pleural fluid or cerebrospinal fluid) were collected from the microbiology laboratories and medical records departments of all hospitals that treat children in the Louisville area, for 1997–2002. Trends in case rates for all cases of invasive S. pneumoniae disease from 1999 to 2002 were observed, and demographic and other factors regarding this illness were recorded for each patient.The trend for rates of invasive pneumococcal disease showed a significant decrease during the study period for all ages combined (P < 0.001), for children younger than 2 years of age (P = 0.002) and for children 2 to 5 years of age (P = 0.002). The mean age for children was 2.22 years, with a male/female ratio of 1.8:1. The most common final diagnoses for the patients were bacteremia without focus, pneumonia and meningitis. Forty-eight percent of the organisms were resistant to penicillin. There was a significantly higher rate of resistance to penicillin among S. pneumoniae strains that caused cerebrospinal fluid infection than among strains that caused non-cerebrospinal fluid infection (P < 0.001). The case fatality rate was 2.6%.Case rates for invasive S. pneumoniae disease among children decreased significantly in the 2-year period after introduction of the heptavalent S. pneumonia protein conjugate vaccine into this community.