Four drug regimens for treating onchocerciasis were compared in a double-blind study in persons from an endemic area in southern Mexico. 40 men were randomly assigned to receive either diethylcarbamazine (DEC) (200 mg/day), mebendazole (2 g/day), levamisole (150 mg per week), or mebendazole plus levamisole. DEC produced the most rapid fall in skin microfilaria counts, but by 6 months the two groups receiving mebendazole showed similar or slightly greater reductions. Despite the administration of corticosteroids to persons receiving DEC, more systemic side-effects were seen in this group. Ocular complications were also commoner and more severe in those receiving DEC. The reduction in the number of intraocular microfilariae at 6 months was similar to those receiving DEC and mebendazole, alone or in combination with levamisole. Levamisole alone had no significant effect on microfilaria counts. Examination of adult worms in nodules excised at 2 months showed changes suggestive of an interruption of embryogenesis in those persons receiving the mebendazole-containing regimens only. The findings suggest that mebendazole may be a useful alternative to DEC in the treatment of onchocerciasis.