The lymphatic filarial parasites, Brugia and Wuchereria, continue to present an immunological puzzle, particularly with respect to the development of natural resistance or damaging disease. We have approached this question by examining humoral responses to a few defined antigens of selected interest from these parasites, using sera from each category in the spectrum of filarial disease. Many antigens, such as the major adult surface protein of Mr 29,000 (29K), appear to be recognized at all stages of infection, but two components show interesting patterns of differential recognition. A triplet of proteins of Mr 65-75K associated with the microfilarial surface is preferentially bound by serum from patent microfilaraemic infections, whereas an unrelated 75K protein has been found to react only with antibody from amicrofilaraemic individuals. In general, however, the data obtained so far emphasize the importance of undertaking an antigenic analysis at the level of single epitopes. Such studies are now under way using recombinant proteins expressed in bacterial hosts.