To determine whether abnormal metabolism of L-fucose in hepatocellular carcinoma is accompanied by alterations in the activities of fucosyltransferases, the latter were determined in plasma and liver tissue of patients with this disease and in cirrhotic and normal subjects. Activities of alpha-2/alpha-3 and alpha-6-L-fucosyltransferases were all significantly greater in plasma from patients with hepatocellular carcinoma than in plasma from cirrhotic patients or normal subjects (p less than 0.025). The activity of each enzyme was dependent, to a similar extent, on Mn2+, Mg2+ and triton X-10, irrespective of the source, and all displayed pH optimums in the range of 7.5 to 8.0. In contrast, activities of alpha-2/alpha-3 fucosyltransferases were significantly lower (p less than 0.025) in homogenates prepared from tumorous liver tissue than in that prepared from nontumorous tissue from hepatocellular carcinoma and cirrhotic patients, whereas for the alpha-6 enzyme the situation was reversed (typically, tumor tissue levels were 5 pmol/hr/mg; in nontumor tissue they were 2 pmol/hr/mg). Activities of galactosyl and mannosyltransferase in tumor tissue were greater in all cases than in nontumor cirrhotic tissue. Plasma fucosyltransferases are specifically elevated in hepatocellular carcinoma but different mechanisms appear to underlie the changes seen for alpha-2/alpha-3 and alpha-6-L-fucosyltransferases.