Small but significant variations in clinical biochemical indices may be of great biological significance. Earlier studies conducted on small, chronically ill, hospitalized, anemic, and/or malnourished population samples suggested associations between body size and composition and indices of iron metabolism, serum protein, and plasma cholesterol. We studied a large, nonhospitalized probability sample of women and men in the First US Health and Nutrition Examination Survey (NHANES I) to characterize these associations. Greater weight, stature, body mass index (BMI), skinfold thickness, and lean body mass (LBM) are associated with higher hemoglobin, hematocrit, and total iron-binding capacity. LBM and body fat are weakly related to serum albumin concentrations in men and to serum total protein concentrations in women. Total cholesterol concentrations are directly associated with weight, body fat, and LBM and are more strongly associated with central than peripheral obesity. Constitutional factors may be important for clinical assessment and for interpretation of epidemiologic studies.