In order to assess the relevance of conformation for the antigenic site A of the hemagglutinin of influenza virus we synthesized two peptides, comprising two variant sequences of the central part of site A (amino acids 140 - 146 of subunit HA1) inserted into an artificial peptide skeleton, which imposes a loop-like structure on the respective sequence stretch. Assuming that the loop structure in the synthetic peptides would roughly approximate to the structure of the cognate protein sequence we tried to raise protein-reactive anti-peptide antibodies. The antibodies obtained indeed showed reactivity against influenza virus, although the discriminating specificity with regard to a mutation at position 144 was lost for virus binding in contrast to the highly specific peptide binding. Considering the failures in raising anti-hemagglutinin antibodies against the site A by immunization with short flexible peptide our results support the hypothesis that conformation makes a major contribution to the immunogenic and antigenic characteristics of site A in influenza hemagglutinin.