Bluetongue virus (BLU), an orbivirus, is of importance to the sheep and cattle industries. We have obtained 5 United States BLU-17 isolates which have been tested for virulence in sheep and 16 BLU-17 field isolates from the Caribbean and Central America. Using a panel of 15 monoclonal antibodies (MAb) against an avirulent BLU-17, we observed that 6 MAbs had negligible or very low neutralization titers for the virulent isolates in contrast to moderate to high titers for the avirulent isolates. These MAbs also differentiated the field isolates into two groups--inadequate vs effective neutralization. All 6 MAbs immunoprecipitated the outer capsid protein, VP2. Electropherotyping of genomic RNA from all 21 viruses identified an increase in RNA segment 3 mobility for those isolates which were not neutralized by the 6 specific MAbs. RNA segment 3 codes for the inner core protein, VP3. There were no detectable electrophoretic differences for RNA segment 2, which encodes VP2. In summary, the virulent BLU-17 isolates differed from the avirulent isolates in both the antigenicity of the outer capsid protein, VP2, and the electrophoretic mobility of RNA segment 3, and we hypothesize that one or both of these changes may result in BLU virulence.