This study evaluated the impact of influenza and vaccination coverage in Apulia, Italy, during the 2004 - 2005 and 2005 - 2006 seasons, using epidemiological and virological surveillance data collected through the Italian Net of Surveillance of Influenza (InfluNet) organized by the Superior Institute of Health (ISS) and the Inter-University Centre of Research on Influenza (CIRI). Vaccination coverage was calculated from the number of doses administered to individuals aged >or= 65 years. Sentinel physicians reported weekly influenza-like illness (ILI) and acute respiratory illness (ARI) occurrences among patients. Influenza viruses were isolated and identified by cell culture on Madin-Darby Canine Kidney cells and polymerase chain reaction techniques. Vaccination coverage reached 72.7% and 77.0% during the 2004 - 2005 and 2005 - 2006 seasons, respectively. Incidence of ILI was higher during the 2004 - 2005 season compared with the 2005 - 2006 season, whereas the incidence ARI appeared to show a more constant trend. Incidence rates for ILI and ARI were higher in the 0 - 14-year age group. The increase in vaccination coverage and implementation of a network of epidemiological and virological surveillance are fundamental for the control and prevention of influenza.