Filarial nematodes are important and widespread parasites of animals and humans. We have been using the African bovine parasite Onchocerca ochengi as a chemotherapeutic model for O. volvulus, the causal organism of`river blindness' in humans, for which there is no safe and e¡ective drug lethal to adult worms. Here we report that the antibiotic, oxytetracycline is macro¢laricidal against O. ochengi. In a controlled trial in Cameroon, all adult worms (as well as micro¢lariae) were killed, and O. ochengi intradermal nodules resolved, by nine months' post-treatment in cattle treated intermittently for six months. Adult worms removed from concurrent controls remained fully viable and reproductively active. By serial electron-microscopic examination, the macro¢laricidal e¡ects were related to the elimination of intracellular micro-organisms, initially abundant. Analysis of a fragment of the 16S rRNA gene from the O. ochengi micro-organisms con¢rmed them to be Wolbachia organisms of the order Rickettsiales, and showed that the sequence di¡ered in only one nucleotide in 858 from the homologous sequence of the Wolbachia organisms of O. volvulus. These data are, to our knowledge, the ¢rst to show that antibiotic therapy can be lethal to adult ¢lariae. They suggest that tetracycline therapy is likely to be macro¢lari-cidal against O. volvulus infections in humans and, since similar Wolbachia organisms occur in a number of other ¢larial nematodes, against those infections too. In that the elimination of Wolbachia preceded the resolution of the ¢larial infections, they suggest that in O. ochengi at least, the Wolbachia organisms play an essential role in the biology and metabolism of the ¢larial worm.