OBJECTIVE To determine the role of an immunodominant antigen OvPG-1 in human onchocerciasis. METHODS Cross-sectional study of subjects living in three onchocerciasis endemic areas. METHODS Mbonge and Tubah divisions of Western Cameroon and in Esmeralda Province of Ecuador. METHODS There were 94 and 99 subjects from the Cameroon rain forest and savannah respectively, and 83 endemic residents from Ecuador. RESULTS The IgG2 anti-OvPG-1 responses of visually impaired and microfiladermic patients were significantly higher than for their age and sex matched counterparts with normal vision and no microfiladermia (p=0.024). Furthermore, the isotype specificity of anti-OvPG-I responses varied for the various onchocerciasis endemic zones. IgG1, IgG2, IgG3 and IgE levels correlated with the presence of microfilariae in Cameroon, but not in Ecuador. CONCLUSIONS Increased IgG and IgE levels to the antigen OvPG-1 seem to correlate with the development of onchocercal eye pathology. The present results suggest that the OvPG1 is a dominant antigen of Onchocerca volvulus with a significant role in the pathogenesis of onchocerciasis.