Avian influenza A virus subtype H5N1 was transmitted to domestic cats by close contact with infected birds. Virus-specific nucleic acids were detected in pharyngeal swabs from 3 of 40 randomly sampled cats from a group of 194 animals (day 8 after contact with an infected swan). All cats were transferred to a quarantine station and monitored for clinical signs, virus shedding, and antibody production until day 50. Despite unfamiliar handling, social distress, and the presence of other viral and nonviral pathogens that caused illness and poor health and compromised the immune systems, clinical signs of influenza did not develop in any of the cats. There was no evidence of horizontal transmission to other cats because antibodies against H5N1 virus developed in only 2 cats.