Evidence is presented that monoclonal antibody BA-1, directed against a marker (CD24) of human lymphocytes of B cell lineage, recognizes a sialic acid-dependent epitope. This conclusion is based on a series of experiments exploiting the reaction of this antibody with bovine and ovine submaxillary mucins. Expression of the epitope was enhanced following alkaline saponification of bovine submaxillary mucin, which converts O-acetylated neuraminic acid residues to N-acetylneuraminic acid. The epitope was destroyed following neuraminidase or mild acid treatment of the mucins, and its expression was diminished following neuraminidase treatment of B lymphoblastoid cells. Glycopeptides obtained by digestion of the bovine mucin with papain, trypsin or pronase were lacking in antigenicity. However, antigenic activity could be regenerated after conjugation of pronase glycopeptides to poly-L-lysine. These results indicate that multivalent display of sialo-oligosaccharide on peptide rather than a protease-susceptible polypeptide domain is required for BA-1 antibody binding.