To determine whether infection with Loa loa could be prevented in temporary residents of endemic areas, we conducted a randomized, double-blind, placebo-controlled trial of diethylcarbamazine as a chemoprophylactic agent. Diethylcarbamazine (300 mg) or placebo was taken orally once a week by Peace Corps volunteers serving in Gabon, Cameroon, and the Central African Republic. The participants were assessed clinically and with serologic and parasitologic testing before and yearly during their two years of service. One hundred one persons satisfactorily completed the study. In Gabon (where exposure to the parasite was heaviest), 6 of 20 volunteers (30 percent) in the placebo group had clinical disease, as compared with none of 16 (0 percent) in the diethylcarbamazine-treated group (P less than 0.02). Of those taking placebo, 10 of 20 (50 percent) became seropositive for antifilarial IgG antibody, as compared with 2 of 16 (12 percent) in the drug-treated group (P less than 0.02). Exposure to the parasite appeared to be much lower among the 65 Peace Corps volunteers in Cameroon and the Central African Republic. No volunteer in either group in these countries had overt loiasis; 2 of 40 (5 percent) in the placebo groups in Cameroon and the Central African Republic seroconverted, as compared with none of 25 (0 percent) of those receiving diethylcarbamazine. Occasional nausea was the only symptom significantly associated with the prophylactic drug regimen. We conclude that diethylcarbamazine given orally once weekly can be an effective, acceptable chemoprophylactic agent to prevent loiasis in temporary residents of regions of Africa where Loa loa is endemic.