Abstract: ObjectiveTo investigate the vicissitudes of influenza virus subtype H3 in Shaoguan by the viriation of hemagglutinin HA1 domain of influenza A virus. MethodsRecovered the influenza virus strains by MDCK cell, Virion RNA were extracted and amplified by RT-PCR, The PCR were purified and test gene sequence, Edit the sequences by Bio-edit、DNA Start. Then compare and analyse the sequences using Clustal-W、Bio-edit、Treeview software. ResultsFour strains had tested, sequence analysis showed that the HA1 domain of these strains had 91.3%-93.8% homology with the vaccine strain A/Panama/2007/1999, 14 amino acids variation was observed in 5 antigenic deteminants, 6 amino acids variation in RBS, and one more glycosylation site at different site in each strain; Compared with the vaccine strain A/Fujian/411/2002,the homology was 90.2%-97.7%,18 amino acids variation was observed in 5 antigenic deteminants,10 amino acids variation was observed in RBS, and there was one more glycosylation site in strains A/SG/199/1999 and A/SG/y009/2008; Compared with the vaccine strain A/Wisconsin/67/2005, the homology was 88.3%-98.4%, 14 amino acids variation was observed in 5 antigenic deteminants,9 amino acids variation was observed in RBS, one more glycosylation site at different site in each strain; The mutation rate decrease gradually in these strains, the most two active amino acid site was in B and D antigenic determinant respectively. ConclusionThere were three times antigen drift of influenza virus subtype (H3) were occurred in Shaoguan between 1999-2008, they were in 1999, 2002 or 2003, 2007 respectively; every variation had 3-4 years intervals. The trend of the antigen drift of influenza virus subtype(H3) strengthen from the situation of 2008.