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Coevolutionary relationships between herbivores and poisonous plants are described. Hepatic detoxification reactions (Phase I and Phase II) are discussed in the context of susceptibility and resistance to poisonous plants. Animal species differences in susceptibility to poisonous plants are discussed, with a comparison of liver vs rumen microbe detoxification pathways. It is concluded, especially with regard to pyrrolizidine alkaloids, that species differences are due to differences in hepatic metabolism rather than to rumen microbes. Linkages between hepatic detoxification abilities and feeding behavior are proposed, as an evolutionary strategy allowing animals resistant to particular toxins to evolve feeding responses to exploit food resources containing toxins to which the animal is resistant.