The highly pathogenic avian influenza virus (HPAIV) subtype H5N1 threatens animal and human health worldwide. Susceptibility of pigeons to HPAIV (H5N1) and their role in avian influenza virus transmission to domestic birds and humans remain questionable. In this study, an outbreak in domestic pigeons (1 to 18 months old) with 50% mortality was investigated. Pigeons exhibited nervous manifestations and greenish diarrhoea. Necropsy of the naturally infected pigeons revealed congestion of the internal organs, particularly the lungs and brain. The HPAIV subtype H5N1 designated A/Pigeon/Egypt/SHAH-5803/2011 was isolated from a 40-day-old pigeon. Sequencing of the haemagglutinin gene showed it to be closely related to viruses in group 2.2.1/C. Intravenous inoculation of the isolate in chickens induced 100% mortality within 2 days post inoculation and the intravenous pathogenicity index was 2.7. Virus pathogenicity and transmissibility was determined experimentally in 6-week-old domestic pigeons. Thirty per cent of pigeons inoculated oronasally with 10(6) median embryo infective dose showed congested beak, conjunctivitis, depression, and greenish diarrhoea. A mortality rate of 10% was recorded preceded by severe neurologic signs consisting of torticollis, incoordination, tremors, and wing paralysis. Pathological examination revealed a friable brain tissue and congested meningeal blood vessels. The lungs appeared oedematous and severely haemorrhagic. Subepicardial and petechial haemorrhages on the coronary fat were observed. Both infected and contact pigeons shed virus via the oropharynx and cloaca. To our knowledge, this is the first description and characterization of HPAIV in naturally infected pigeons in Egypt. Our findings reveal that pigeons can indeed be susceptible to H5N1 HPAIVs and could be a source of infection to other birds and humans.