Aberrant expression of blood group antigens has been observed in human cancers. Lewis(x) (Le(x)) and Lewis(y) (Le(y)) antigens are usually absent from parenchymal cells in the adult human liver, but frequently expressed on cholangiocarcinomas and less frequently on hepatocellular carcinomas. Little information is available on the distribution of these antigens in fetal livers. We studied five livers each from the first, second, and third trimesters, and infants by an immunohistochemical method on paraffin-embedded sections, using monoclonal antibodies to Lex and Le(x) antigens. Le(x) was seen in the bile duct epithelium of four out of five second and four of five third trimester fetal livers and in all the neonatal livers. Hepatocytes and bile duct epithelium of first trimester livers were negative. Le(y) staining of bile duct epithelium was present in all second and third trimester fetal livers and infant livers. Staining of hepatocytes was seen in four of five first, three of five second, two of five third trimester livers, and one of five infant livers. These observations suggest that the expression of Le(x) on hepatocytes decreases with gestational age and that the frequency of Le(x) and Le(y) expression in cholangio- and hepatocellular carcinomas follows that of fetal livers.