Clinical, parasitological and serological diagnostic methods were compared for de initive diagnosis of human onchocerciasis in three endemic communities o Nkpologu, Ukpabi and Obimo; located at d f ering distances from the bank of Adada river in Nsukka senatorial zone of Enugu State, Nigeria. The results revealed that 43.98%, 2.78%, 57.60% and 76.55% o the total number o volunteers tested were positive by most common and rare clinical symptoms, skin biopsy and Enzyme-linked immunosorbent assay (ELISA) respectively. O those seropositive, 86.02% had microfilariae in their skin. Similarly, 67.28% and 91 91% o those who were pos tive by ELISA and skin biopsy respective y displayed onchocercal nodules either on the head trunk, groin, laps or near the knee. However, 96.76% of those with nodules had microfilariae in their skin. The results further showed that the inc dence o onchocerciasis and worm burden in the three communities vary inversely with their respective d s ances from the river. Considering the relative significance of these methods in the diagnosis of onchocerciasis, we recommend the use o a combination of the most common clinical manifestations, skin biopsy and ELISA in the diagnosis of onchocerciasis, at least for epidemiological studies, until a single definitive diagnostic method is developed.