To assess the filaricidal activity and clinical safety of albendazole in human loiasis, a double-blind, placebo-controlled study was conducted in an endemic area in Benin, Africa. Twenty-three men with microfilaremia (100-30,000/mL) were randomly assigned to receive albendazole (200 mg; n = 11) or placebo (n = 12) twice daily for 21 days; 1 patient from each group withdrew from the study. There were no clinical adverse effects and no observed hepatotoxicity, renal toxicity, or hematologic abnormalities attributable to the drug. In the albendazole group, microfilarial levels began to decrease at day 14 after treatment and by 6 months had fallen to a geometric mean of 20% of pretreatment levels (vs. 84.8% in the placebo group). Blood eosinophil levels and anti-filarial IgG and IgG4 also fell significantly in response to albendazole. Taken together, these data suggest that albendazole has a primary (possibly embryotoxic) effect on the adult parasite, resulting in a slow decrease in microfilaremia.