The avermectins are macrocyclic lactones produced by fermentation of the soil micro-organism Streptomyces avermitilis. They show activity against a broad range of nematodes and arthropod parasites of domestic animals at dose rates of 300 microgram/kg or less. Unlike the macrolide or polyene antibiotics, they lack significant antibacterial or antifungal activity. By oral or parenteral administration, avermectins are active against gastrointestinal nematodes and lungworms, and important ectoparasites such as lice, mange mites, ticks and larval stages of flies. They show excellent activity against parasites resistant to existing anthelmintics or ectoparasiticides. The avermectins appear to cause paralysis of nematodes and arthropods by opening gamma-aminobutyric acid-mediated chloride channels at the neuromuscular junction.