In order to study the levels of cross-reactivity of the influenza virus-specific antibody response upon infection or vaccination, usually hemagglutination inhibition assays are performed. In the present study post-infection ferret sera and serum samples obtained from cynomolgus macaques which were vaccinated with an ISCOM preparation based on the influenza virus strain A/Netherlands/18/94 (H3N2) were analyzed for cross-reactivity in the hemagglutination inhibition assay and in virus neutralization assays. It was shown that the cross-reactivity of the antibodies induced upon vaccination or infection with influenza virus proved to be more limited in the virus neutralization assay than in the hemagglutination assay. The strong antibody response induced by vaccination with the A/Netherlands/18/94-ISCOM preparation was shown to be cross-reactive with recent influenza virus strains, which were isolated since 1992, but not with older strains.