Cell type-specific expression of specific carbohydrate structures on cell surface glycoproteins and glycolipids is increasingly recognized for providing information relevant to cell-cell interactions in developing and adult organisms. Sialyltransferases contribute to the diversity in carbohydrate structure through their attachment of sialic acid in various terminal positions on glycolipid and on glycoprotein (N-linked and O-linked) carbohydrate groups. In this report, differential expression of five sialyltransferase genes in human tissues is evaluated as a potential mechanism to account for cell type-specific variation in terminal sialoside structures produced by a cell. For this analysis, the complete cDNA of the human Gal beta 1,3GalNAc alpha 2,3-sialyltransferase and a partial cDNA of the developmentally regulated STX gene were cloned. Northern analysis was performed using these cDNAs and those of three previously cloned human sialyltransferase genes as probes. Each of the five sialyltransferase genes exhibits dramatic differential expression in the 16 adult and 5 fetal human tissues examined, and expression of each gene appears to be independently regulated. Comparison with fragmentary earlier studies of the expression of several of the same enzymes in rat tissues suggests that the overall pattern of expression is largely conserved.