Numerous species of ticks and mites (collectively known as acarines) are serious pests of animals, humans, and crops. There are few commercially available acaricides and major classes of these chemicals continue to be lost from the marketplace due to resistance development or deregistration by regulatory agencies. There is consequently a pressing need to isolate new and safe acaricidal compounds. In this study, we show that two families of peptide neurotoxins isolated from the venom of the Australian funnel-web spider Hadronyche versuta are lethal to the lone star tick Amblyomma americanum. These toxins, which are specific blockers of arthropod voltage-gated calcium channels, induce a pronounced phenotype characterized by an unusual gait that is rapidly followed by paralysis and death. Remarkably, one of these toxins, the calcium channel blocker omega-atracotoxin-Hv1a, is virtually equipotent whether the toxin is injected or fed to A. americanum.