In Cameroon, a 3-year randomized, double-blind controlled trial was conducted to determine if ivermectin, given at 3-monthly intervals and/or at high doses (800 microg/kg), had a greater effect on adult Onchocerca volvulus than standard annual doses of 150 microg/kg. Adverse reactions were recorded and analysed in a logistic regression model with random effects to assess the influence of the dose and rhythm of treatment on their occurrence. After the first dose, 3-monthly treatment was associated with a clearly reduced risk of reactions, especially oedematous swellings, pruritus and back-pain. Oedematous swellings and subjective ocular troubles were found to be associated with high doses of ivermectin. These results reinforce former parasitological conclusions that it would be desirable to evaluate the feasibility and effects on transmission of large-scale 3-monthly treatments with standard doses of ivermectin for onchocerciasis control. Owing to the unexpected ocular reactions, the use of high doses to counteract any future resistance of O. volvulus to ivermectin should be considered with caution.