Nineteen monoclonal antibodies produced to dengue type 4 virus (DEN-4) strain 4328-S were tested for their ability to mediate antibody-dependent infection enhancement (ADE) with seven DEN-2 strains in P-388D1 mouse macrophage-like cells. In this first study of the distribution of enhancing epitopes on multiple DEN-2 strains reacted with monoclonal antibodies to a different serotype (DEN-4), DEN-4 monospecific antibodies produced ADE with DEN-2 viruses, indicating the presence of DEN-4-like determinants on DEN-2 viruses. Analysis differentiated at least one and possibly more DEN-2 strain subgroups, one of which (isolates AHF-110 and AHF-191) was previously identified by DEN-2 monoclonal antibody analysis. The study demonstrates the heterogeneous distribution of dengue complex and DEN-4 epitopes on DEN-2 strains. Monoclonal antibodies are valuable tools for study of the biology of ADE and its relation to dengue shock syndrome.