A total of 742 sedentary subjects were recruited, initially tested, exercise-trained in the laboratory with the same program for 20 weeks, and re-tested. The subjects came from families of Caucasian descent with both parents and three biological adult offspring and families of African-American ancestry. Oxygen uptake, expiratory volume and respiratory exchange ratio, blood pressure, heart rate, blood lactate, glucose, glycerol and free-fatty acids, stroke volume and cardiac output were measured during exercise before and after training and maximal oxygen uptake was determined. Plasma lipids, lipoproteins and apoproteins, glucose tolerance and insulin response to an intravenous glucose load, plasma sex steroids and glucocorticoids, resting systolic and diastolic blood pressures, and body fat and regional fat distribution were also assessed. Dietary habits, level of habitual physical activity and other lifestyle components were assessed by questionnaires. Genetic analyses included the determination of the heritability level for each phenotype and its response to regular exercise, testing for the presence of paternal or maternal effects, sex-limited effects, major gene effects and segregation patterns. Multivariate genetic analyses and complex segregation analyses were used to develop hypotheses concerning the genetic basis of the response to exercise-training.