We examined the relation between coffee consumption and levels of serum total cholesterol, high-density-lipoprotein (HDL) cholesterol, and triglycerides in a population of 7213 women and 7368 men between the ages of 20 and 54 years. Coffee consumption was positively associated with levels of total cholesterol and triglycerides in both sexes and was inversely associated with levels of HDL cholesterol in women. The coffee-cholesterol relation remained strong and statistically significant (P less than 0.0001 in a covariance analysis) after adjustment for age, logarithm of body-mass index, physical activity in leisure time, cigarette smoking, and alcohol consumption. After adjustment for all covariates, the total cholesterol level was 5.56 +/- 0.05 mmol per liter (mean +/- S.E.) in men drinking less than one cup of coffee a day, as compared with 6.23 +/- 0.03 mmol per liter in those consuming more than nine cups a day. The corresponding figures for women were 5.32 +/- 0.05 and 5.92 +/- 0.04 mmol per liter. None of the other variables considered could explain this relation. We conclude that coffee consumption is a major contributor to the variation in levels of total cholesterol.