Naturally occurring cases of influenza in cats owing to the H5N1 strain have been reported in several countries. A cat reservoir of H5N1 in the United States could provide an environment for zoonotic disease spread to humans. This scenario was the impetus to develop a model to study potential transmission of H5N1 virus in domestic cats utilizing information on cat ownership and cat–cat interaction patterns, in addition to biological properties of the virus. The roaming behaviour of cats significantly influenced epidemic dynamics, as demonstrated by the simulation results from this model. A better understanding of the behaviour of domestic cats and the H5N1 influenza virus can be used to predict epidemic dynamics following the introduction of H5N1 virus into the United States and to develop effective strategies to prevent virus transmission to both cats and humans.