AIMS: To study the association between alanine aminotransferase (ALT) and the 6-year risk of the metabolic syndrome in a population-based study in Caucasian men and women. METHODS: The association of ALT with the 6-year risk of the metabolic syndrome in 1097 subjects, aged 50-75 years, was assessed in the Hoorn Study with logistic regression analysis. Subjects with the metabolic syndrome at baseline, defined according to the Adult Treatment Panel III of the National Cholesterol Education Program, were excluded. RESULTS: After 6.4 (range 4.4-8.1) years follow-up, 226 subjects (20.6%) had developed the metabolic syndrome. The odds ratio (95% confidence interval) for developing the metabolic syndrome, adjusted for age, sex, alcohol intake and follow-up duration was 2.25 (1.50-3.37) for subjects in the upper tertile compared with those in the lower tertile of ALT. This association persisted after additional adjustment for all the baseline metabolic syndrome features [1.62 (1.02-2.58)]. Among the individual components of the metabolic syndrome, ALT was significantly associated only with fasting plasma glucose at follow-up. CONCLUSIONS: These data suggest that ALT is associated with risk of the metabolic syndrome in a general population of middle-aged Caucasian men and women, further strengthening the role of ALT as an indicator for future metabolic derangement. These findings warrant further studies to elucidate the role of non-adipose tissue fat accumulation in the pathogenesis of complications related to the metabolic syndrome.