Sequentially collected sera from Mongolian jirds (Meriones unguiculatus) infected with Brugia malayi and B. pahangi were tested for antibodies to homologous and heterologous antigens by the enzyme-linked immunosorbent assay (ELISA). Titers were <1:100 prior to infection and rose rapidly (within 2 weeks). Peak titers were observed prior to patent microfilaremia, and high titers persisted during infection. Use of the homologous antigen did not increase sensitivity or specificity of the ELISA. In fact, B. malayi-infected jirds demonstrated higher titers to the heterologous antigen, B. pahangi, than to the homologous antigen. Fractionation of B. malayi antigen over a wide pH range using isoelectric focusing did not eliminate cross-reactions, but the reactions of 20 B. malayi sera and 20 B. pahangi sera tested more strongly to specific fractions, particularly in the lower pH range.