A total of 556 individuals in Agbalenyi Community of Oji-River local government area of Enugu State, Nigeria were studied using questionnaires, focus group discussions and key informant interviews to determine the socio-cultural factors affecting the transmission of onchocerciasis. The result revealed a low level of knowledge about the cause, prevention and complications of onchocerciasis. Respondents have developed a cultural system around the disease due to long exposure. The majority are aware of the disease which they recognize once their body starts itching or musculoskeletal pain develops but only 64.4, 34.0, 1.4 and 3.6%, respectively attributed chronic itching, nodules, bad vision and leopard skin to blackfly bite. Other perceived causes mentioned include ageing, the type of food eaten, farm work and 'bad blood'. Only 0.8% knew diagnosis could be made through skin snips. Neither Oji-River nor any of the river systems were associated with any of the complications of onchocerciasis. Significant differences in most socio-demographic characteristics were associated with differences in the level of knowledge about the disease.