Populations of eastern red-backed salamanders, Plethodon cinereus, exhibit color polymorphism, and two color morphs are common: the red-striped morph and the lead-phase morph. A recent hypothesis attributes the maintenance of the polymorphism to selection on behavior and physiology. We conducted a series of laboratory experiments and a field study to determine whether striped and lead-phase salamanders exhibit different antipredator responses and whether predators differentially attacked the color forms. In predation trials, red-striped salamanders spent significantly more time in an “all trunk raised” posture and tended to remain immobile, whereas lead-phase salamanders were significantly more mobile. In field collected museum specimens of individual P. cinereus, we found more lead-phase salamanders with autotomized tails compared to red-striped salamanders, possibly indicating different attack rates on the two forms. The results from this study demonstrate that striped and lead-phase salamanders of P. cinereus respond differently to snake predators and may be attacked differently in the field. These differences may contribute to the maintenance of color polymorphism in this species.