Most clinicians and researchers view serum gamma-glutamyltransferase (GGT) activity as a measure that can be interpreted equally in patients regardless of their demography. The present study evaluates the concurrent influence of age and body mass index (BMI) on GGT in a sample of 133 high functioning young men, with detailed assessment of the pattern of alcohol use at ages 20 [time 1 (T1)], 30 [time 2 (T2)], and 35 [time 3 (T3)]. GGT increased between T1 and T2 (15.4 +/- 9.65 units/liter vs. 20.1 +/- 12.07 units/liter, t = 4.17, p < 0.001), and between T2 and T3 (20.1 +/- 12.07 units/liter vs. 27.3 +/- 24.69 units/liter, t = 4.11, p < 0.001). Controlling for drinking quantity and frequency did not change the finding. The relationship between GGT and BMI was estimated after splitting the sample into normal (BMI < or = 25 kg/m2) and overweight (BMI > 25 kg/m2) subjects. The correlation between GGT and BMI in normal weight men at T1 was r = 0.15, p = 0.09, at T2 r = 0.00, p = 0.96, and at T3 r = 0.09, p = 0.09. In overweight subjects, correlation at T1 was r = 0.40, p = 0.20, at T2 r = 0.36, p < 0.05, and at T3 r = 0.44, p < 0.001. Controlling for the effect of alcohol consumption and/or age did not alter these conclusions. Testing for the interaction of age, BMI, and alcohol consumption did not yield relevant results. We concluded that GGT is positively related to age in the 20s to late 30s and to BMI in overweight subjects; both relationships of age and BMI were independent of alcohol consumption. The interpretation of GGT should take age and BMI into account when suspecting subclinical alcohol problems in young men.