Captive sea otters (Enhydra lutris)fed live Saxidomus giganteus (butter clams) ad libitum either reduced their prey capture and consumption rates or discarded the highly toxic siphons and kidneys when switched from clams containing very low levels of saxitoxin [37±9 µg STX (100 g)−1] to highly toxic clams [226±96 µg STX (100 g)−1]. Feeding rates returned to pretreatment levels when the otters were again switched to low‐toxicity clams, but siphon discard frequency remained high. Paralytic shellfish poisoning symptoms were observed only in an otter calculated to have consumed the most STX (154 µg kg−1 d−1), a dosage within the range of oral LD50s reported for other nonprimate mammals. None of the other otters displayed symptoms, and all subjects were eventually released in good health. These findings suggest that otters are not immune to paralytic shellfish poisoning toxins (PSPT) and that they have the ability to detect and avoid consumption of lethal amounts of toxic prey. This behavioral response is highly adaptive given the importance of butter clams in sea otter diets, and the chronic toxicity of butter clams in areas where toxic dinoflagellate blooms occur. A comparison of the distributions of otters and toxicity levels of butter clams in southeast Alaska suggests that the sequestering of PSPT may protect some clam populations from otter predation and limit the distribution of otters to the exposed outer coast where toxic clams are rare.