The ocular changes that occur with diethylcarbamazine treatment of onchocerciasis seriously restrict its usefulness. Ivermectin, a newly developed antifilarial drug, was compared with diethylcarbamazine for treatment of onchocerciasis in a double-masked, placebo-controlled trial. Thirty men with moderate to severe infection and ocular involvement were randomly assigned to receive ivermectin as a single oral dose (200 micrograms/kg), diethylcarbamazine (administered for eight days), or placebo. Detailed ocular examinations were performed serially over a 12-month period. Diethylcarbamazine treatment caused a marked increase in living and dead microfilariae in the cornea, punctate opacities, and limbitis during the first week of therapy. Ivermectin had no such effect. However, ivermectin therapy resulted in a long-term reduction in intraocular microfilariae comparable to that seen with diethylcarbamazine. Ivermectin appears to have few ocular complications and be a better-tolerated and more effective microfilaricidal agent than diethylcarbamazine for the treatment of onchocerciasis.