Specific diagnosis of antibodies to Onchocerca was achieved through (1) the construction of direct and indirect ELISA systems, and (2) restricting ELISA assays to the IgG4 class. The direct ELISA was based on the isolation of a surface derived, low molecular weight surface antigen preparation containing two main antigens (M. wt. 16.2 and 12.8 kDA) as defined by Western blot analysis. The direct ELISA system detected antibodies in children of six years old, and may therefore be applicable to detecting reinvasion in OCP areas of Onchocerca volvulus control. The indirect ELISA system was a competitive binding ELISA-based assay using a monoclonal antibody recognising two Onchocerca components (M. wts. 15.6 and 25.9) on a Western blot. The direct and indirect ELISA systems were similarly specific and sensitive when evaluated in a preliminary survey. The direct ELISA system yielded a specificity and sensitivity of: 100% and 100% respectively, using Mexican endemic and Mexican intestinal nematode infection sera as positive and negative controls respectively: 91% and 96% respectively, using Venezuelan endemic and Venezuelan Mansonella ozzardi infection sera as positive and negative controls, respectively: 87% and 93% respectively, using African endemic and Papuan (New Guinea) Wuchereria bancrofti infection sera as positive and negative controls respectively: 93% and 93% respectively, using African endemic and Indian W. bancrofti infection sera as positive and negative controls respectively. Similar specificity and sensitivity levels were obtained when the same comparisons were made using the indirect (inhibition) ELISA assay. These values may be contrasted with the currently used PBS extract of O. volvulus which yielded specificities of less than 10% in all the above comparisons.(ABSTRACT TRUNCATED AT 250 WORDS)