Lewis(x) is a cell-surface carbohydrate antigen defined by the trisaccharide structure, Gal beta 1-->4 (Fuc alpha 1-->3) GlcNAc. Expression of Lewis(x) and sialyl-Lewis(x) antigens in primary cell cultures isolated from fetal human brains of 12-15 weeks gestation was investigated by double immunolabelling with antibodies against monomeric Lewis(x) (4C9), oligomeric Lewis(x) (FH4), and sialylated oligomeric Lewis(x) (FH6) antigens and cell type-specific markers. The monomeric Lewis(x) antigen was expressed in more than 15% of astrocytes and 100% of oligodendrocytes, whereas it was not identified in neurons or in microglia. The oligomeric Lewis(x) antigen was undetectable in any cell types, while the sialylated oligomeric Lewis(x) antigen was expressed in more than 95% of microglia but not in any other cell types. The cell type-specific expression of Lewis(x) and sialyl-Lewis(x) antigens in fetal human glial cells suggests that these fucose-containing carbohydrate molecules play roles in intercellular recognition between distinct cell types during the development of the human central nervous system.