We have isolated a major sialoglycoprotein on leucocytes and found that this glycoprotein, termed leukosialin, is ubiquitously present on various human leucocytes (granulocytes, monocytes/macrophages and T lymphocytes). Our studies showed that leukosialin is significantly glycosylated by O-linked oligosaccharides (70 chains/molecule). The polypeptide portions of these molecules are, however, apparently the same, with a molecular mass of 38.5 kDa. The amino acid sequence derived from cDNA shows tandemly repeated O-glycan attachment sequences, and about 70% of the serine or threonine residues in the external domain are modified by O-glycans. The structures of those O-linked oligosaccharides are characteristic of each cell lineage and maturation stage. In particular, we have shown that O-glycans of leukosialin are converted from NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-6)]-GalNAc to NeuAc(alpha 2-3)Gal(beta 1-3) [NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(beta 1-6)] GalNAc during T cell activation.