As an approach to determine the functional role of the carbohydrate moieties of complement components, the interaction between functionally pure human (Hu) or guinea pig (GP) components and several lectins with differing sugar specificities has been studied. Hu and GP components 1 through 9 were screened for exposed sugar residues by interaction with lectins immobilized by covalent binding to Sepharose 4B. The remaining fluid phase activity of individual components was determined by titration using an appropriate indicator system. The lectins used in this study were castor bean type II (CB II), phytohemagglutinin (PHA), lotus bean (LB), wheat germ agglutinin (WGA) and soy bean (SB). Of the lectins tested, CB II, WGA, PHA, and SB removed fluid phase GP or Hu C1 activity. In addition, CB II bound to Sepharose 4B interacted with Hu or GP C4 and C2. None of the lectins interacted with any component beyond C2 in the classical complement pathway.