Monoclonal antibodies specific for eight antigenic sites on the G1 glycoprotein of La Crosse virus were studied in a kinetics of neutralization assay. When examined at the same protein concentration, there were differences in the rates and degree of neutralization induced by these antibodies. The maximum amount of neutralization detected in antibody excess ranged from 1.5 to 3 logs. Another 2 to 3 logs of viral infectivity could be neutralized by the addition of polyclonal anti-G1 antibody or a second monoclonal antibody. However, only certain pairs of monoclonal antibodies enhanced the neutralization the additional 2 to 3 logs. The antibody pairs enhancing neutralization were those also found to be synergistic in a competition binding assay (L. Kingsford, L. D. Ishizawa, and D. W. Hill, 1983, Virology 129, 443-455) as well as any neutralizing antibody used in combination with antibodies to epitopes within one particular site on the glycoprotein. The data indicate that antibody binding to two different specific sites on G1 is needed to neutralize La Crosse virus to the same extent that is observed with polyclonal antibody.