A cyclic disulfide peptide representing antigenic site A of foot-and-mouth disease virus (FMDV) strain C-S8c1 (residues 134 to 155 of viral protein 1 (VP1) with Tyr136 and Arg153 replaced by cystine; TTCTASARGDLAHLTTTHACHL) was synthesized by solid phase methods. Formation of the cyclic disulfide was carried out by air oxidation of the fully deprotected and reduced bis-cysteine precursor, under high dilution conditions. The identity of the cyclic peptide was confirmed by both physical and enzymatic methods. A conformational study of the cyclic peptide and of its linear parent structure (YTASARGDLAHLTTTHARHLP, residues 136-156 of VP1 of FMDV C-S8c1) by circular dichroism in the presence of a structure-inducing solvent showed the cyclic disulfide analog to adopt lower levels of alpha-helix than its linear counterpart. In competitive ELISA assays both peptides reacted with similar affinity against a representative panel of neutralizing monoclonal antibodies directed towards antigenic site A. Thus, a high inherent flexibility of this loop may preclude a conformational restriction strong enough to alter recognition by anti-virus antibodies.