This report describes the presence of circulating Onchocerca volvulus antigens (COA) in sera of patients with onchocerciasis. By using a double diffusion immunoelectrophoresis method, COA could be detected in 24 of 77 sera analyzed (31%). In contrast, when more sensitive assays such as the radioimmunoprecipitation-PEG assay or sandwich radioimmunoassay were used to detect COA, about 75% of the sera from O. volvulus-infected patients were found positive; moreover, a highly significant correlation between the two assays was observed. The parasite specificity of the COA was demonstrated directly by identity reaction with a component of O. volvulus somatic antigens. COA was never found when hyperimmune antisera against other parasite antigenic extracts were used instead of anti-O. volvulus hyperimmune serum. However, when anti-O. volvulus hyperimmune serum was used against sera obtained from patients infected with various other helminths we found a cross-reactivity between COA and the circulating antigens of other human filarids (Wuchereria bancrofti, Loa loa, Brugia malayi), but not with other nematode or trematode parasites (Ascaris lumbricoides, Schistosoma mansoni, Fasciola hepatica). Further immunoelectrophoretic studies demonstrated one precipitin arc localized in the cathodic region which seemed specific for COA, which raises the possibility of preparing a monospecific hyperimmune serum to circumvent cross-reactivities.