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Complete genome sequences of H5N1 viruses derived from a domestic cat “A/Cat/Thailand/KU-02/04” and dog “A/Dog/Thailand/KU-08/04” were comprehensively analyzed and compared with H5N1 isolates obtained during the 2004 and 2005 outbreaks. Phylogenetic analysis of both cat and dog viruses revealed that they are closely related to the H5N1 viruses recovered from avian influenza outbreaks of the same period. Genetic analysis of 8 viral gene segments showed some evidence of virulence in mammalian species. In summary, the H5N1 viruses that infected a domestic cat and dog are highly pathogenic avian influenza viruses that are virulent in mammalian species, potentially indicating transmission of H5N1 viruses from domestic animals to humans.