Midazolam, a water soluble benzodiazepine derivative, inhibited the motility of Onchocerca volvulus microfilariae in vitro at concentrations of 25, 50, and 100 µg/ml. The effect was proportional to the concentrations used. Microfilariae regained motility after elimination of midazolam by washing. Diethylcarbamazine did not alter the midazolam effect. It is suggested that the Mazzotti reaction as the sequelae of diethylcarbamazine is caused by transient increased microfilarial migration. Combining midazolam with the diethylcarbamazine medication may prevent the Mazzotti reaction.