Four peptides have been synthesized, corresponding to different regions of the H3 influenza hemagglutinin, that are related to antigenic sites "A" and "B" of the molecule. The peptides consisted of the following sequences: 139-146, which forms the "loop" in the native hemagglutinin molecule, with either glycine or aspartic acid at position 144; 147-164, which contains part of antigenic determinant "B"; and 138-164, which comprises both the loop and the area 147-164. The peptides were conjugated to tetanus toxoid and used for immunization of rabbits and mice. All four conjugates elicited an immune response against the homologous peptides, but only the peptides 138-164 and 147-164 gave rise to antibodies that recognized and bound to the intact virus. Protection of mice against challenge infection with A/Eng/42/72 virus was achieved only by immunization with the conjugate (138-164)-TT, which led to partial protective effect. These data emphasize the role of molecular structure in determining the antigenic properties of synthetic peptides and indicate that the length of the peptide could be crucial for enforcing the right folding required to mimic the native structure.