OBJECTIVE: This article examines characteristics of a subgroup of alcohol dependent men with very elevated serum Gamma-Glutamyltransferase (GGT) activity. METHOD: GGT was measured in 196 men soon after admission to an inpatient alcohol and drug treatment program. Subjects were split into two groups based on the a priori GGT value of > or =150 U/L for Group 1 (n = 20), and <150 U/L for Group 2 (n = 176). Serum aspartate amino-transferase (AST), serum alanine amino-transferase (ALT) and mean corpuscular volume (MCV), as well as several aspects of the drinking history, were compared cross-sectionally between the two groups. The stability of GGT in the context of drinking was evaluated prospectively over 12 months in a subsample of 35 individuals. RESULTS: Most measures of the drinking pattern and severity of dependence were similar between the two groups, although subjects in Group 1 demonstrated higher levels for AST (p < .01), MCV (p < .01) and ALT (p < .01). Subjects in Group 1 reported more drinking days per month (23.8 +/- 3.98 vs 17.8 +/- 8.71, t = 5.43, p < .001), and more related history of alcoholic liver disease (30.0% vs 8.5%, chi2 = 8.66, p < .01). In the presence of the variables significantly different between the two groups, AST, the number of drinking days per month and the proportion with alcoholic liver disease predicted membership to Group 1, although their influence was moderate (pseudo R between 0.16 and 0.20). The correlation between GGT at intake and follow-up in 35 individuals who returned to drinking was r = .56, p < .001, while two out of three subjects with high GGT at intake were also high at follow-up. CONCLUSIONS: Subjects with very high GGT seem to demonstrate a more intense vulnerability to alcohol, a characteristic which appears to be stable over time.