Natural antibodies to self and non-self proteins, including dietary proteins, are a significant part of the immune repertoire of humans. Antibodies to three structurally related legume lectins (Erythrina corallodendron lectin (ECorL), peanut agglutinin (PNA), and soybean agglutinin (SBA)) and to one cereal lectin (wheat germ agglutinin (WGA)) were purified by affinity chromatography from human sera and their binding specificity examined. The anti-SBA, anti-ECorL and anti-WGA antibodies exhibited high specificity, whereas the anti-PNA antibodies were polyreactive. Although the anti-WGA antibodies were highly specific for WGA, they also crossreacted slightly toward some other proteins. The anti-ECorL antibodies bound to native SBA, but the anti-SBA antibodies failed to bind to the native ECorL. Although the anti-SBA and anti-ECorL antibodies both exhibited specificity when interacting with native lectins, they bound to a wider range of denatured lectins, indicating a common or universal epitope which is recognized by many natural antibodies. Interestingly, the natural antibodies did not interfere with the agglutination properties of the lectins. These findings may provide a basis for studying the in vivo biological effects of anti-dietary protein antibodies, including those against carbohydrate-binding proteins.