Recently avian influenza A viruses of the H5N1 subtype were shown to infect humans in the Hong Kong area, resulting in the death of six people. Although these viruses did not efficiently spread amongst humans, these events illustrated that influenza viruses of subtypes not previously detected in humans could be at the basis of a new pandemic. In the light of this pandemic threat we evaluated and compared the efficacy of a classical non-adjuvanted subunit vaccine and a vaccine based on immune stimulating complexes (ISCOM) prepared with the membrane glycoproteins of the human influenza virus A/Hong Kong 156/97 (H5N1) to protect roosters against a lethal challenge with this virus. The ISCOM vaccine induced protective immunity against the challenge infection whereas the non-adjuvanted subunit vaccine proved to be poorly immunogenic and failed to induce protection in this model.