Relationships between weight, height and ponderal indexes and plasma high-density lipoprotein (HDL) cholesterol and triglyceride were assessed by the Lipid Research Clinics Prevalence Study for 6865 white children and adults (3517 males and 3348 females). Overall, weight, weight/height, weight/height and weight/height were significantly and inversely associated with plasma HDL cholesterol levels and positively associated with plasma triglyceride levels. When the relationships of Quetelet index (weight/height) to HDL cholesterol were assessed by multiple regression analysis, including the explanatory variables of cigarette smoking, alcohol intake and exogenous estrogen hormone use, the Quetelet index was significantly and inversely associated with HDL cholesterol levels in children (by age 12-16 years) and adults of both sexes. After covariance adjustment for smoking, alcohol intake, hormone use and age, mean HDL cholesterol levels for individuals at the Quetelet tenth percentile were 3 mg/dl higher than for those at the fiftieth percentile, and these in turn were 3-4 mg/dl higher than for those at the ninetieth percentile. These differences in HDL cholesterol differences reported to be related to coronary heart disease mortality. Improved approaches to the primary prevention of atherosclerosis may be realized by a better understanding of the inverse relationship of body mass to HDL cholesterol levels.