An IgM lambda cold agglutinin reacted preferentially with newborn (i cord) and i adult erythrocytes. The whole serum of patient Vo and the antibody isolated by warm elution reacted moderately with native and neuraminidase-treated red cells but strongly with papainized red cells. Papainization of erythrocytes enhanced markedly the susceptibility of the corresponding antigen not only to antibody binding but also to the action of neuraminidase, indicating that sialic acid is the immunodominant component of the cryptic antigen. The cold agglutinin Vo is the first example of a human monoclonal antibody recognizing a sialic acid-dependent, developmentally regulated antigen fully expressed on newborn erythrocytes.