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Serum total and low-density lipoprotein (LDL) cholesterol contribute significantly to atherosclerosis and its clinical sequelae. Previous analyses of data from the National Health and Nutrition Examination Surveys (NHANES) showed that mean levels of total cholesterol of US adults had declined from 1960–1962 to 1988–1994, and mean levels of LDL cholesterol (available beginning in 1976) had declined between 1976–1980 and 1988–1994.To examine trends in serum lipid levels among US adults between 1960 and 2002, with a particular focus on changes since the 1988–1994 NHANES survey.Blood lipid measurements taken from 6098 to 15 719 adults who were examined in 5 distinct cross-sectional surveys of the US population during 1960–1962, 1971–1974, 1976–1980, 1988–1994, and 1999–2002.Mean serum total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and geometric mean serum triglyceride levels, and the percentage of adults with a serum total cholesterol level of at least 240 mg/dL (≥6.22 mmol/L).Between 1988–1994 and 1999–2002, total serum cholesterol level of adults aged 20 years or older decreased from 206 mg/dL (5.34 mmol/L) to 203 mg/dL (5.26 mmol/L) (P = .009) and LDL cholesterol levels decreased from 129 mg/dL (3.34 mmol/L) to 123 mg/dL (3.19 mmol/L) (P<.001). Greater and significant decreases were observed in men 60 years or older and in women 50 years or older. The percentage of adults with a total cholesterol level of at least 240 mg/dL (≥6.22 mmol/L) decreased from 20% during 1988–1994 to 17% during 1999–2002 (P<.001). There was no change in mean HDL cholesterol levels and a nonsignificant increase in geometric mean serum triglyceride levels (P = .06).The decrease in total cholesterol level observed during 1960–1994 and LDL cholesterol level observed during 1976–1994 has continued during 1999–2002 in men 60 to 74 years and women 50 to 74 years. The target value of no more than 17% of US adults with a total cholesterol level of at least 240 mg/dL (≥6.22 mmol/L), an objective of Healthy People 2010, has been attained. The increase in the proportion of adults using lipid-lowering medication, particularly in older age groups, likely contributed to the decreases in total and LDL cholesterol levels observed. The increased prevalence of obesity in the US population may have contributed to the increase in mean serum triglyceride levels.