A 92-kDa fusion protein that encodes amino acids 1-479 of a 62-kDa Brugia malayi antigen induces resistance to microfilariae in mice. The antigenicity of this recombinant protein was explored in asymptomatic residents of Wuchereria bancrofti-endemic areas of Papua New Guinea and Egypt. Unlike sera from individuals in nonendemic areas, sera from residents of endemic areas contained IgG3 antibodies (up to dilution 1:1280) reactive with the fusion protein. There was little or no recombinant antigen-specific IgG1, IgG2, IgG4, or IgE. The mean level of IgG3 antibodies to the amino acid 1-479 construct in sera of putatively "immune" adult Papua New Guineans and children in whom microfilaremia was < 4 parasites/mL of blood was not significantly different (P < .05) from those with > 1000 parasites/mL. These data indicate that the filarial antigen corresponding to the recombinant protein is highly immunogenic in naturally infected children and adults and that the isotype and magnitude of antibody reactivity with it do not correlate with the microfilaremic status of asymptomatic persons.