It has been shown that a light-to-moderate intake of alcohol may enhance insulin sensitivity; a decrease in insulin sensitivity is a component of the clustering of risk factors known as the metabolic syndrome. However, previous studies have been limited to relatively small or heterogeneous study groups, or have used suboptimal methods of measuring insulin action. Hence the aim of the present study was to examine whether the metabolic syndrome (as recently defined),components of this syndrome and smoking are associated with alcohol consumption. The study was performed in a population-based sample of clinically healthy men (n=391), all 58 years old and not undergoing any treatment with cardiovascular drugs. Insulin-mediated glucose uptake (euglycaemic hyperinsulinaemic clamp) was measured in a subgroup of these subjects (n=104). Trend analysis showed no difference in alcohol intake across the groups of men with none of the criteria in the definition of the metabolic syndrome (n=77),men with one or more of the criteria (n=252) and men fulfilling all criteria (n=62). However, in the whole group (n=391), alcohol consumption was significantly positively associated with serum triacylglycerols (triglycerides), high-density lipoprotein (HDL) cholesterol and cigarette-years. Furthermore, alcohol consumption was positively associated with insulin-mediated glucose uptake (r=0.20, P<0.05). In multiple regression analyses, body mass index, alcohol consumption and serum triacylglycerols were independent co-variates to insulin-mediated glucose uptake. Thus, in 58-year-old healthy men recruited from the general population, there was a significant association between alcohol consumption, serum triacylglycerols, HDL cholesterol and cigarette-years. In a subgroup of 104 subjects, alcohol consumption was independently and positively associated with insulin-mediated glucose uptake. To our knowledge, this is the first study to show an independent relationship between insulin sensitivity, as measured by the clamp technique, and alcohol intake.