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High-density lipoprotein (HDL)-cholesterol levels, inversely related to the risk of myocardial infarction, are determined by genetic and environmental factors. The aim of this study was to evaluate the prevalence of low and high HDL plasma levels and the influence of environmental factors and lipid profile in an Italian non-smoker female population. HDL, apolipoprotein A-I, apolipoproteins, lipids and estrogen plasma levels were measured in a population of 1471 women with a mean age of 45±14 years. HDL values ≤35 mg/dl were noted in 11.2% of the subjects, showing 2.4% coronary heart disease (CHD) prevalence. The 90th percentile was characterized by HDL levels ≥66 mg/dl and the absence of coronary atherosclerosis. Total cholesterol, apolipoprotein B and triglycerides (r=−0.31, p<0.0001) were the main determinants of HDL levels; apolipoprotein E, estrogen use, body mass index (BMI), alcohol consumption and age showed a weaker correlation. Apolipoprotein A-I concentration was influenced more notably by estrogen use, total cholesterol and apolipoprotein E; levels of triglycerides, apolipoprotein B, BMI, age and alcohol consumption are less important. The parameters considered here, taken together, explain HDL and apolipoprotein A-I variability of approximately 31% and 24%, respectively. A surprisingly high prevalence of very low (≤35 mg/dl) and high (≥66 mg/dl) HDL levels in Italian women further confirms the importance of studies on the HDL distribution in different population groups.