To analyse the epidemiological and molecular features of a long-lasting epidemic (12 weeks) of influenza in north-eastern Italy during the 2004–05 season. Morbidity rates were analysed by time and age. Influenza virus isolates (93 strains) were submitted to antigenic evaluation by haemagglutination inhibition test and to molecular assessment by sequencing. The incidence peak (16.4 per thousand) was the highest recorded over the last six years in north-eastern Italy. The epidemic was sustained by two subsequent waves of circulating viruses: an H3N2 variant and two type B variants, respectively. In addition, scattered isolation of an H1N1 variant occurred. Antigenic and molecular characterisation showed the emergence of an H3N2 virus drifted with respect to vaccine strain, which also had a substantial impact on morbidity in vaccinated subjects. Moreover, a single K145N substitution in the HA1 site of H3N2 was the starting point of two evolutionary branches.
