Ophthalmic examinations on 6831 individuals aged 5 years or more, living in 34 guinea savannah communities mesoendemic for onchocerciasis, in Kaduna State, Nigeria, revealed a relatively high prevalence (9%) of optic nerve disease (OND). Further investigations were performed to determine what proportion of this burden of OND might be due to onchocercal infection. Information on history of cerebro-spinal meningitis (CSM), past use of diethylcarbamazine (DEC) and chloroquine, consumption of cassava and locally produced alcohol was collected for all individuals by questioning. In addition, a nested case-control study of 81 cases of OND and 136 age and sex-matched controls was performed to investigate whether syphilis or a variety of other neurological disorders were responsible for a substantial proportion of cases of OND. Our data suggest that in this population, onchocercal infection is the single most important cause of OND and may account for 50% of all cases. Some 13% of cases were associated with signs suggestive of glaucoma. DEC use might be responsible for up to 30% of all OND. We found no evidence to suggest that any of the following are important causes of OND in the communities studied: CSM, syphilis, neurological syndromes such as polyneuropathy or other generalized neurological disease, consumption of raw cassava, consumption of locally prepared alcohol.