The serum level of alpha-L-fucosidase activity has been suggested as a useful marker in the diagnosis of hepatocellular carcinoma, although the precise mechanism behind the elevation of this parameter has not been determined. We found that the serum alpha-L-fucosidase activity level was significantly higher in 67 patients with hepatocellular carcinoma (695.1 +/- 245.5 nmol/ml/hr) than in 47 patients with cirrhosis (389.1 +/- 188.2 nmol/ml/hr; p < 0.001) and in 54 controls (202.0 +/- 104.6 nmol/ml/hr; p < 0.001). However, alpha-L-fucosidase activity was not correlated with tumor size (r = 0.134), whereas the alpha-fetoprotein level was correlated with tumor size (r = 0.580, p < 0.001). When 515.8 nmol/ml/hr was taken as the cutoff value (mean value in the controls plus 3 standard deviations), alpha-L-fucosidase activity was above the cutoff value in 12 of the 17 patients with a hepatocellular carcinoma less than 2 cm in diameter, in 28 of the 37 patients with a hepatocellular carcinoma less than 3 cm in diameter and in 52 of the 67 patients with hepatocellular carcinoma. In contrast, only 10 of the 47 patients with cirrhosis had levels above the cutoff value. These findings suggest that an increase in serum alpha-L-fucosidase activity in patients with cirrhosis may be a marker for detecting a hepatocellular carcinoma, especially a small tumor, because alpha-fetoprotein and des-gamma-carboxy-prothrombin are less promising as tumor markers.