As of May 19, 2009, a total of 5,469 confirmed or probable cases of human infection with a novel influenza A (H1N1) virus had been documented in 47 states and the District of Columbia. In addition, the virus had spread to 41 countries, with a total of 4,774 cases reported in countries outside the United States. Because producing a novel influenza A (H1N1) virus vaccine will take several months, determining whether receipt of seasonal influenza vaccine might offer any protection against the novel influenza A (H1N1) virus is important. Therefore, using stored serum specimens collected during previous vaccine studies, CDC assessed the level of cross-reactive antibody to the novel influenza A (H1N1) virus in cohorts of children and adults before and after they had been vaccinated with the 2005-06, 2006-07, 2007-08, or 2008-09 influenza season vaccines. The results indicated that before vaccination, no cross-reactive antibody to the novel influenza A (H1N1) virus existed among children. Among adults, before vaccination, cross-reactive antibody was detected in 6%--9% of those aged 18--64 years and in 33% of those aged >60 years. Previous vaccination of children with any of four seasonal trivalent, inactivated influenza vaccines (TIV) or with live, attenuated influenza vaccine (LAIV) did not elicit a cross-reactive antibody response to the novel influenza A (H1N1) virus. Among adults, vaccination with seasonal TIV resulted in a twofold increase in cross-reactive antibody response to the novel influenza A (H1N1) virus among those aged 18--64 years, compared with a twelvefold to nineteenfold increase in cross-reactive antibody response to the seasonal H1N1 strain; no increase in cross-reactive antibody response to the novel influenza A (H1N1) virus was observed among adults aged >60 years. These data suggest that receipt of recent (2005--2009) seasonal influenza vaccines is unlikely to elicit a protective antibody response to the novel influenza A (H1N1) virus.