Secondary metabolites play an important role in host plant resistance to insects, and insects, in turn, may develop mechanisms to counter plant resistance mechanisms. In this study, we investigated the toxicity of gramine to the cereal aphid Sitobion avenae and some enzymatic responses of S. avenae to this alkaloid. When S. avenae fed on an artificial diet containing gramine, mortality occurred in a dose-dependent manner. The LC(50) of gramine was determined to be 1.248 mM. In response to gramine, S. avenae developed increased activities of carboxylesterase and glutathione S-transferase, two important detoxification enzymes. The activities of both enzymes were positively correlated with the concentration of dietary gramine. In addition, the activities of peroxidase and polypheolic oxidase, two important oxidoreductase enzymes in S. avenae, increased in response to gramine; however, catalase activity decreased when insects were exposed to higher levels of dietary gramine. The potential role of gramine in host plant resistance and S. avenae counter-resistance is discussed.