Using a panel of new monoclonal antibodies (mAbs), five neutralizing, conformation-dependent sites have been identified on the antigenic variant of swine vesicular disease virus (SVDV) circulating currently. In studies on the antigenic conservation of these sites, the four antigenic/genetic groups of SVDV described showed distinguishable patterns, confirming this classification. By sequencing mAb-resistant mutants, the five sites have been mapped precisely and localized on a three-dimensional model of the SVDV capsid. All were found to be orientated, to a different extent, towards the external surface of the capsid. Three of the five sites, located in VP1, VP2 and VP3, correspond to epitopes identified previously in historic isolates as sites 1, 2a and 3b, respectively. Another site, site IV, which maps to position 258 of VP1, corresponds to an epitope reported recently and is described in this study to be specific for isolates of the most recent antigenic group of SVDV. A fifth site is described for the first time and corresponds to the unique neutralizing site that is common to both SVDV and coxsackie B5 virus; it maps to positions 95 and 98 of VP1, but may also include positions nearby that belong to site 1 on the BC-loop of VP1, suggesting the classification of site Ia. These results may have useful diagnostic and epidemiological applications, since mAbs to the new conserved site Ia provide universal reagents for SVDV detection systems, while the specificity of mAbs to site IV make them unique markers for the most recent strains of SVDV.