Neotropical poison frogs (Dendrobatidae) contain a variety of lipophilic alkaloids in their diffusely distributed cutaneous glands, including a major class of compounds known as pumiliotoxins. Pumiliotoxins are highly toxic and are believed to protect frogs against predators. Their potential activity against ectoparasites, however, has not been investigated. We tested female yellow fever mosquitoes (Aedes aegypti) for responses to 8-hydroxy-8-methyl-6-(2'-methylhexylidene)-1-azabicyclo[4.3.0]nonane, designated pumiliotoxin 251D [PTX (+)-251D], a skin alkaloid present in all genera of dendrobatids and in other anurans, and to its unnatural enantiomer, PTX (-)-251D. Both enantiomers of PTX 251D presented on silicone feeding membranes reduced landing and feeding by A. aegypti, but PTX (+)-251D did so at lower concentrations. PTX (+)-251D also induced toxicosis, shown when mosquitoes failed to fly off membranes. Similarly, mosquitoes confined with copper wires coated with PTX (+)-251D exhibited greater latencies to fly off the substrate and a higher incidence of leg autotomy than did those confined with the (-)-enantiomer. Our results on the contact toxicities of PTX 251D enantiomers parallel those reported for mice injected with them. The presentation of serial dilutions of PTX (+)-251D to A. aegypti revealed a minimum toxic concentration of 0.1 microg/cm2. This value is substantially lower than that estimated for the cutaneous abundance of this compound in some frogs, an observation consistent the function of PTX 251D in anuran chemical defense against ectoparasitic arthropods.