The antifilarial action of 2-[2-(4-hydroxyphenyl)-6-benzimidazolyl]-6-(1-methyl-4-piperazyl) benzimidazole (HOE 33258) was investigated in Mastomys natalensis infected with Litomosoides carinii. The subcutaneous administration of HOE 33258 in a single daily dose for 5 consecutive days, or at other intervals, produced, depending on the dosage, a rapid reduction in the number of microfilariae in the circulating blood. The reduction amounted to more than 90% within 7-14 days after the treatment was started or at the end of the dosage schedule. The small, slow increase in the microfilarial count during a period of 6-7 weeks after treatment ended reached not more than half the number present before treatment. HOE 33258 showed marked activity on the reproductive system of mature female worms, although only few macrofilariae were killed by the drug. The results also demonstrated the usefulness of L. carinii infection of M. natalensis as a model for the evaluation of the filaricidal activity of drugs.