Carbohydrate-deficient transferrin (CDT) measurements have been widely examined as a marker of excessive alcohol consumption, yet the information on the sensitivity of this method has remained controversial. In addition, little is known of the relationship of this marker and the severity of alcoholic liver disease (ALD). To clarify these issues, we analyzed serum samples from 373 alcohol abusers, including 200 problem drinkers with no apparent liver pathology, 173 patients with clinical or morphological evidence of ALD, and 42 healthy controls. CDT was analyzed by anion-exchange chromatography followed by radioimmunoassay. At a specificity of 100%, the sensitivity of CDT was 36% in problem drinkers reporting a mean of 710 +/- 80 (mean +/- 2SE) g of ethanol/week, as compared with the sensitivities of 44% and 35% for gamma-glutamyltranspeptidase (GGT) and mean corpuscular volume (MCV), respectively. In a subgroup of problem drinkers (n = 51) with the highest ethanol intakes (1160 +/- 180 g of ethanol/week) and severe dependence, the sensitivity of CDT increased to 64%, compared with 55% for GGT and 39% for MCV. In ALD, the CDT values were significantly higher than in the alcoholics with nonliver pathology. However, when such patients were classified according to the clinical, laboratory, and morphological severity of liver disease, CDT was found to be primarily elevated in those with the early stage of ALD, such that there was a significant negative correlation between CDT and the combined morphological index of disease severity (rs = -0.315, p < 0.05). ALD markers of fibrogenesis were elevated more frequently than CDT, showing significant positive correlations with the indices of disease severity.(ABSTRACT TRUNCATED AT 250 WORDS)