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Abstract: To investigate the frequency of amantadine resistance among influenza A viruses isolated in Korea during the 2003–2009 seasons, 369 (16.8%) 2199 A/H1N1 viruses and 780 (14.8%) of 5263 A/H3N2 viruses were randomly selected. The M2 and HA1 genes of each isolate were amplified by reverse transcription-polymerase chain reaction and followed by nucleotide sequencing. The results showed that the resistance rate to amantadine among A/H1N1 viruses increased significantly from 2004–2005 (33.3%) to 2007–2008 (97.8%) and then decreased dramatically in 2008–2009 (1.9%). The A/H1N1 isolates recently detected in 2008–2009 turned amantadine-sensitive containing two new substitutions at specific sites (S141N, G185A) in HA1. Compared with A/H1N1 viruses, the amantadine resistance among the A/H3N2 viruses increased from 2003–2004 (9.7%) to 2005–2006 (96.7%) and decreased in 2006–2007 (57.4%). During 2006–2007, both of amantadine-resistant and -sensitive A/H3N2 viruses co-circulated but clustered in different branches phylogenetically. All of A/H3N2 isolates tested during 2007–2009 appeared to cluster in the same group being resistant to amantadine. [Copyright &y& Elsevier]