We investigated the cardiovascular effects of lifelong passive cigarette smoke exposure in preadolescent children and examined the following questions: 1) Is systemic oxygen transport altered? 2) Are coronary heart disease risk factors adversely affected? We recruited 216 families from the MCV Twin Study; 105 had at least one smoking parent. Serum thiocyanate and cotinine levels were used as measures of smoke exposure in the children and thiocyanate was proportional to the number of parental cigarettes smoked each day (p = 0.0001). Paternal smoking had no effect on these measures. Whole blood 2,3-diphosphoglycerate was higher in smoke-exposed than unexposed children (p < 0.01) and was related to the thiocyanate level (p < 0.02). High density lipoprotein (HDL) cholesterol was lower in passive smoking children (p < 0.05); the HDL2 subfraction was reduced in passive smoking boys, while the HDL3 subfraction was reduced in passive smoking girls. Significant adverse alterations in systemic oxygen transport and lipoprotein profiles are already present in preadolescent children exposed to long-term passive cigarette smoke, primarily from maternal smoke. Children with long-term exposure to passive smoke may be at elevated risk for the development of premature coronary heart disease.