Antigenic site A is supposed to be ideal for antibody binding and for amino acid replacements [33] . The preferred antigenic site in the change from A/Moscow/10/ 99(H3N2) to A/Fujian/411/02(H3N2)-like viruses was site B. This observation is in accordance with previously published data [39] . One region in HA, position 225 to 227, that influence antigenic site D, has changed drastically during the study period from GVS → DVS → DIP → NIP. The influence of antigenic site D was first apparent in the antigenic change from Fujian-like viruses to California-like viruses; however, the antigenic site B was still the preferred site for antigenic change. It has been proposed that a minimum of four substitutions in two or more antibody binding sites are required for an epidemically important strain [40] . 