Previous studies of chemoreceptive behavior in vipers suggest that snakes focus on the scent of envenomated tissue to track their prey following envenomation. Other studies have indicated a correlation between qualitative differences in venom biochemistry and geographic variation in diet. The North American copperhead (Agkistrodon contortrix) varies geographically in diet and venom biochemistry; snakes were collected from three populations (Kansas, Texas, and Louisiana) that are known to have different prey preferences. Behavioral experiments were conducted to assess whether copperheads preferred envenomated prey more than nonenvenomated prey, as do other species of vipers studied thus far. Additional experiments tested the ability of copperheads to distinguish between envenomated prey from different geographic populations, and between geographic populations of copperheads and two other species of viper. Results indicated that copperheads prefer envenomated prey to nonenvenomated prey. In envenomated-prey discrimination experiments, copperheads distinguished between envenomated prey from different geographic populations, and some snakes distinguished envenomated prey of A. contortrix from those of A. piscivorns and Sistrurus catenatus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to study the variation of venom biochemistry in this species and two other taxa (A. piscivorus and S. catenatus), and confirmed intraspecific and interspecific variation of venom proteins. Relative potency of the venom from different populations as indicated by time to immobilization experiments was in the order: Louisiana > Texas > Kansas. The relative potency of the venom from each population matched the order of preference in the chemoreception experiments. These results suggest that chemoreception is sensitive to subtle differences in venom biochemistry and may reflect adaptation to improve efficiency of finding envenomated prey.