H2 influenza viruses have not circulated in humans since 1968 and therefore a large segment of the population would likely be susceptible to infection should H2 influenza viruses re-emerge. The development of a H2 pandemic influenza vaccine candidate should therefore be considered a priority in pandemic influenza preparedness planning. We selected a group of geographically and temporally diverse wild-type H2 influenza viruses and evaluated the kinetics of replication and compared the ability of these viruses to induce a broadly cross-reactive antibody response in mice and ferrets. In both mice and ferrets, A/Japan/305/1957 (H2N2), A/mallard/NY/1978 (H2N2) and A/swine/MO/2006 (H2N3) elicited the broadest cross-reactive antibody responses against heterologous H2 influenza viruses as measured by hemagglutination-inhibition and microneutralization assays. These data suggested that these 3 viruses may be suitable candidates for development as live attenuated H2 pandemic influenza vaccines.