The HERITAGE family study (HEalth, RIsk factors, exercise Training And GEnetics) will document the role of the genotype in the cardiovascular, metabolic, and hormonal responses to aerobic exercise training. A consortium of five universities in the United States and Canada are involved in carrying out the study. A total of 90 Caucasian families and 40 African-American families with both parents and three or more biological adult offspring are being recruited, tested, exercise-trained in the laboratory with the same program for 20 wk, and re-tested. Oxygen uptake, respiratory exchange ratio, blood pressure, heart rate, cardiac output, blood lactate, glucose, and free-fatty acids are measured during exercise, and maximal oxygen uptake is determined before and after training. Plasma lipids, lipoproteins and apoproteins, glucose and insulin response to an intravenous glucose load, plasma sex steroids and glucocorticoids, and body fat and fat distribution are assessed. Dietary and activity habits and other life style components are assessed by questionnaires, prior to, during, and after training. A variety of genetic analyses will be undertaken, including heritability studies and major gene effects, for each phenotype and its response to regular exercise. Cell lines are established, and DNA sequence variation at a variety of molecular markers will be determined for association and linkage studies.