OBJECTIVE: In this work we assessed the relationship between HDL-cholesterol levels and various inflammation markers status in a sample of cardiovascular disease free adult men and women from Greece. METHODS: The ATTICA study is a population-based cohort that has randomly enrolled 1128 men and 1154 women (aged >18 years old), stratified by age-gender, from the greater area of Athens, during 2001-2002. Adherence to Mediterranean diet was assessed through a diet-score that was based on a validated food-frequency questionnaire. In this study we assessed the relationship between HDL-cholesterol levels and inflammation markers (high sensitivity C-reactive protein, interleukin-6, homocysteine and amyloid-a), after taking into account the effect of several confounders. RESULTS: 46% of men and 40% of women had total serum cholesterol levels >200 mg/dl, while 21% of men and 7% of women had HDL-cholesterol levels <35 mg/dl. The mean value for HDL-cholesterol was 53+/-14 mg/dl in females and 44+/-14 mg/dl in males. HDL-cholesterol levels were inversely correlated to the hs-CRP levels (b=-0.028, P=0.001) and homocysteine levels (b=-0.039, P=0.036), after adjustment for sex, age, body mass index, physical activity status, smoking, total cholesterol levels, lipid lower agents, ethanol intake and diabetes mellitus; while no statistical significance was found between HDL-cholesterol levels and interleukin-6 and serum amyloid-a. CONCLUSIONS: In this work we evaluated the inverse relationship between HDL-cholesterol levels and inflammatory markers in a sample adult cardiovascular disease free population. This study among others illustrates the anti-inflammatory emerging role of HDL-cholesterol in reducing cardiovascular risk.