Queen Snakes (Regina septemvittata) are extreme dietary specialists, feeding nearly exclusively on freshly molted crayfish. To elucidate specific cues that mediate prey detection and foraging behavior in R. septemvittata, we examined the response of R. septemvittata and the dietary generalist Nerodia sipedon sipedon, to chemical compounds produced by crayfish during the molting cycle. Ingestively naive neonate snakes were presented with 20-hydroxyecdysone, ecdysone, methyl farnesoate, ponasterone A, xanthurenic acid, and distilled water. Their response was measured using a modification to the tongue-flick attack score. Regina septemvittata exhibited an elevated tongue-flicking response to ecdysone, whereas N. s. sipedon exhibited no differential responses to these same arthropod molting chemicals. In a second experiment, R. septemvittata showed a two-fold higher tongue-flicking response to intermolt crayfish extract that contained ecdysone than to intermolt crayfish extract alone, whereas N. s. sipedon demonstrated no differential response between these extracts. In a third experiment consisting of feeding trials, R. septemvittata was offered live intermolt crayfish with and without ecdysone. The presence of ecdysone increased the feeding scores of R. septemvittata. When ecdysone was present, crayfish were ingested in five of the seven trials, but when ecdysone was absent crayfish were not ingested in any trial. These results suggest that ecdysone may play a critical role in the interaction between R. septemvittata and their prey. With numerous stream contaminants known to imitate ecdysone and disrupt the arthropod molting cycle, this finding may have important implications for the conservation of R. septemvittata.