On April 21, 2009, CDC reported the first cases of 2009 pandemic influenza A (H1N1) virus infection in the United States. On April 24, in response to those reports, the Chicago Department of Public Health (CDPH) established enhanced surveillance for 2009 pandemic influenza A (H1N1) virus infections. The first cases were identified on April 28. This report summarizes laboratory-confirmed cases identified during April 24-July 25 and provides clinical and epidemiologic data for a subset of those cases. By July 25, a total of 1,557 laboratory-confirmed cases had been reported to CDPH. The overall attack rate was highest among children aged 5-14 years (147 per 100,000 population), which was 14 times higher than for adults aged >or=60 years. A total of 205 (13%) patients were hospitalized, with the highest rate observed among children aged 0-4 years (25 per 100,000), followed by children aged 5-14 years (11 per 100,000). These findings affirm prevention strategies that target children and young adults, who are at a disproportionate risk for infection and hospitalization. The Advisory Committee on Immunization Practices (ACIP) recommends that these populations should be among the first groups targeted for vaccination with influenza A (H1N1) 2009 monovalent vaccine.