Flubendazole, an injectable benzimidazole drug, was compared with diethylcarbamazine (DEC) in a prospective double-blind study of the treatment of onchocerciasis. Nineteen Mexican men were randomly assigned to receive either flubendazole 750 mg intramuscularly once a week for 5 doses, or DEC 100 mg twice daily for 14 days, and they were then followed up for 12 months. Major systemic side-effects during the first 3 weeks were common in the DEC group but not in the flubendazole group in which there was considerable inflammation at the injection site instead. Ocular complications (limbitis, punctate keratitis, and uveitis) were also common in the DEC group, whereas in the flubendazole group they consisted only of one new punctate opacity at day 4 in one subject. One DEC patient also had several new areas of chorioretinal changes on day 2 but these had disappeared by 2 months. Skin microfilaria counts fell rapidly in the DEC group, but returned to the pretreatment levels. In contrast, skin microfilaria counts in the flubendazole group fell slowly, but by 6 and 12 months were lower than in the DEC group (at 12 months 0.2 vs 7.3 mf/mg, p less than 0.001). In addition, by 6 months none of the flubendazole subjects had intracorneal microfilariae, and only one had microfilariae in the anterior chamber, whereas the numbers of intraocular microfilariae in the DEC group had returned to pretreatment levels. The results suggest that flubendazole is safer and more effective than DEC in the treatment of onchocerciasis.