Influenza is a globally important respiratory pathogen that causes a high degree of morbidity and mortality annually. Although current vaccines are effective against virus infection, new strategies need to be developed to satisfy the global demand for an influenza vaccine. To address this point, we have engineered and produced the full-length hemagglutinin (HA) protein from the A/Wyoming/03/03 (H3N2) strain of influenza in plants. The antigenicity of this plant-produced HA was confirmed by ELISA and single-radial immunodiffusion (SRID) assays. Immunization of mice with plant-produced HA resulted in HA-specific humoral (IgG1, IgG2a and IgG2b) and cellular (IFNgamma and IL-5) immune responses. In addition, significant serum hemagglutination inhibition (HI) and virus neutralizing (VN) antibody titers were obtained with an antigen dose as low as 5mug. These results demonstrate that plant-produced HA protein is antigenic and can induce immune responses in mice that correlate with protection.