Ivermectin, given as a single oral dose, has shown considerable promise as a new treatment for onchocerciasis. We assessed the safety and efficacy of ivermectin and tried to determine the optimal dose. Two hundred Liberians received 100, 150, or 200 micrograms of ivermectin/kg or placebo and were followed up for 12 months. Therapy was associated with only minimal systemic and ocular side effects. A 200-micrograms/kg dose was associated with greater systemic reaction than was a 100-micrograms/kg dose. Each treatment group had significant reduction in skin microfilaria counts by day 3 and a decrease of approximately 95% at three months. At three months the proportion of persons with no microfilariae in a specimen of skin was significantly less in the 100-micrograms/kg group than in the 150-micrograms/kg or 200-micrograms/kg groups. At 12 months, the level of microfilariae in skin was still reduced approximately 80%. Significant reduction in ocular involvement was seen in all groups. These results confirm that single-dose ivermectin is effective and well-tolerated and suggest that 150 micrograms of ivermectin/kg may be the optimal dose for initial therapy.