The appearance of desialo-transferrin (De-TF) in serum has been reported to be a biochemical marker of chronic alcoholism. However, conclusive evidence of whether De-TF is a marker for chronic alcohol drinking or for alcoholic liver disease (ALD) has not yet been obtained. Glycoproteins can be divided into two groups, a transferrin (TF) group and an alpha 1-acid glycoprotein (A1-AG) group, based on the characteristics of microheterogeneity (M-HTG) of each protein. In the present study, the appearance of M-HTG in serum TF and A1-AG in alcohol drinkers was compared. In 96 patients with ALD, M-HTG of TF was found in 66 patients (68.8%), and M-HTG of A1-AG was found in 61 patients (63.5%). In 20 patients with alcoholic pancreatitis, the detection rate of M-HTG of A1-AG was significantly higher than that of TF. In six patients with pancreatitis but not liver disease, M-HTG of TF was not detected. In 14 alcoholics without liver or pancreas disease, M-HTG of TF was not detected, whereas M-HTG of A1-AG was detected in 6 cases--a significant difference. The amount of alcohol consumed was not different in patients with and without liver disease. In non-ALD, M-HTG of both proteins was detected only in patients with decompensated liver cirrhosis. The detection rate of M-HTG in TF was significantly higher than in A1-AG. These results suggest that M-HTG of serum TF is a marker of ALD and that of serum A1-AG is a marker of chronic alcohol drinking.