Lectins were included in the first dimension gel in crossed immunoelectrophoresis of human serum proteins. Con A resulted in a retardation of most glycoproteins during the first electrophoresis and heterogeneous forms of individual glycoproteins could be detected. Ulex europeus lectin gave most of the proteins a higher migration velocity. Pokeweed mitogen did not interact with serum glycoproteins, but it did with serum lipoproteins. The method allows a close study of interacting components, determination of binding specificities, and detection of minor interacting components, including heterogeneous molecular forms.