In the February 2006 in two wetlands in northern Iran, the mortality among wild swans was observed. Paralysis was the most prominent feature of the disease. Histologically, diffused necrosis of acinar cells in pancreas, degeneration and necrosis of some neurons in central nervous system (CNS), sever necrotic and hemorrhagic enteritis, foci of haemorrahge and myocardial cell necrosis in the heart, mild to moderate multifocal hepatocytic necrosis, limited focal necrosis in the kidney and testis and morphological evidence of apoptosis in the spleen were observed. Immunohistochemically, influenza virus antigen were detected more often in the acinar cells of pancreas, some neuron and glial cells in CNS, renal tubule of kidney and hepatocytes of the liver. Moreover, antigen was seen in the meisner plexus of the intestine and testis, but seldom in the lung. The RT-PCR tests showed the presence of H5, N1 and NP genes of influenza virus in trachea, lung, liver, kidney, spleen, and cerebellum. Deduced amino acid sequence at cleavage site was PQGERRRKKR G which is typical for highly pathogen avian influenza viruses. The phylogenetic analysis of HA(heamagglutinin) protein showed a very close similarity of Z/101(H5N1) virus with HA proteins of H5 influenza viruses isolates from cat, wild duck, chicken, ostrich and turkey in various geographical regions. Our data confirmed that these new emerging viruses are systemically able to infect wild swans. The high HA protein sequence similarity among H5N1 viruses from various geographical areas of the word shows that the wild aquatic birds are the major cause of worldwide spreading of H5N1 viruses.