A specific serodiagnostic test for onchocerciasis has been a priority objective of the World Health Organization. Fragments of cDNA encoding Onchocerca volvulus antigens selected on the basis of their specificity for this parasite were subcloned into a protein purification and expression system. No individual recombinant antigen showed a high sensitivity in an enzyme-linked immunosorbent assay because of heterogeneity in the response of O. volvulus-infected individuals. However, a cocktail of three recombinant proteins showed 96% sensitivity with 100% specificity, compared with 99% sensitivity and only 59% specificity against a crude O. volvulus extract. The sensitivity of detection of individual antigens varied between sera taken from individuals from different geographic areas infected with O. volvulus, but when used as a cocktail, all but one of the microfilaria-positive individuals from all the geographic areas studied were detected. Recombinant probes provide a practical basis for specific diagnostic tests for helminth infections.