Two toxic and bitter-tasting cardenolides (cardiac-active steroids) were sequestered by the brightly colored oleander aphid,Aphis nerii B. de F., from the neotropical milkweed host plantAsclepias curassavica L. After feeding on milkweed-reared aphids, the orb-web spiderZygiella x-notata (Clerck) built severely disrupted webs and attacked fewer nontoxic, control aphids, whereas the webs of spiders fed only nontoxic aphids remained intact. The regularity and size of the prey-trapping area of webs were reduced significantly in proportion to the amount of toxic aphids eaten. The effects of toxic aphids on spider web structure were mimicked by feeding spiders the bitter-tasting cardenolide digitoxin, a cardenolide with similar steroidal structure and pharmacological activity to the two aphid cardenolides. These results show that the well-known effects of psychoactive drugs on spider web structure are more than interesting behavioral assays of drag activity. Similar effects, produced by plant-derived chemicals in the spider's aphid prey, are relevant to the ecology and evolution of interactions between prey defense and predator foraging.