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To assess adverse effects of ivermectin treatment in a Simulium neavei-transmitted focus of onchocerciasis, a study was conducted with 1,246 patients infected with Onchocerca volvulus in eight villages in western Uganda. Study participants were treated the first time with a single dose of 150 μg/kg of ivermectin. Adverse reactions to ivermectin were determined through questioning and clinical examination during house-to-house visits to the participants within 48 hours after ivermectin treatment. Overall adverse reactions were observed in 737 (59.1%) patients. Severe reactions were rare (10 patients, 1.4%). Our data show that adverse reactions to ivermectin in an S. neavei-transmitted onchocerciasis focus in western Uganda occur frequently. In spite of the fact that many patients showed adverse reactions to ivermectin, the drug was well accepted and appreciated by the population.