Epidemiological surveys indicate that the prevalence of epilepsy is higher in developing countries than in industrialized countries. Except for neurocystocercosis due to Taenia solium, little is known about possible underlying causes. This article reports the relationship between epilepsy and onchocerciasis in an Onchocerca volvulus endemic area in West Uganda. Individuals complaining of seizures were identified by means of a population census in 12 villages. Active epilepsy was confirmed in 61 of 4743 inhabitants (crude prevalence rate = 1.3%; age-standardized rate = 1.1%). Distribution of epilepsy in the study area was clustered, ranging from a prevalence of 0.2% to 3.4% in different villages. Age-specific prevalence was highest between 10 and 19 years, with a rate of 3.6% for the study are as a whole, and up to 10.0% in villages of high epilepsy prevalence. The prevalence of onchocerciasis in the 10-19-year-old age group was assessed by skin-snip biopsy and ranged from 15% to 85% in different villages. Epilepsy was significantly more frequent in the three villages with the highest levels of O. volvulus endemicity than in other villages (P < 0.0001). Serological testing for T. solium infection was positive in one and borderline in three of 53 epilepsy patients tested. The significant correlation between epilepsy and onchocerciasis did not change when these four patients were excluded from the analysis. These findings suggest a strong association between epilepsy and onchocerciasis in this area. This could have significant implications for the concept of morbidity due to O. volvulus.