A recent outbreak of influenza in Hong Kong was caused by a highly virulent virus of avian origin. Concern that the appearance of such a virus in the human population may be a harbinger of a new pandemic has brought increased attention to the issue of antivirals available for treatment of influenza. A/HongKong/156/97 (H5N1), the first virus of H5N1 subtype isolated from a human host, is highly virulent in the mouse model and can infect mouse lungs without requiring adaptation. High mortality and evidence of systemic disease, including spread to the brain after intranasal inoculation, are observed. Zanamivir, a novel neuraminidase inhibitor, is effective at decreasing replication of the virus in vitro. In a model of lethal challenge in mice, zanamivir reduces lung titers of the virus and decreases morbidity and mortality.