An influenza pandemic occurs when an animal-origin influenza virus crosses the species barrier and transmits efficiently from person-to-person via the airborne route. To understand the viral properties that facilitate transmission, a panel of mutant viruses were generated with mutations in the viral protein, hemagglutinin, that binds to cell surface receptors. These viruses were evaluated in a receptor binding assay to determine which mutations enhance the affinity of hemagglutinin for human receptors.