It is indisputable that there is an epidemic of obesity in the U.S. and many other countries. It is equally clear that this has resulted from too many people being in positive caloric balance for too many days, but the specific contributions of energy intake and energy expenditure to this persistent positive caloric balance remain unclear. In fact, some recent authors claim that physical inactivity has virtually no role in the obesity epidemic. Although there is typically an upward trajectory of body weight over the adult years, there also are other patterns of weight variation over time. For physical activity, the general trajectory shows a decline during adulthood;but some increase their activity and others fluctuate multiple times. The patterns of weight change over time, and the role of changing patterns of physical activity, especially in relation to weight, have not been studied extensively. Limitations of current research on patterns of obesity and physical activity are that most experimental studies are relatively short-term and most large observational studies have not examined patterns of change in these exposures and their interrelationships. Moreover, most observational studies use self-reported body weight and activity habits. Therefore, the goal of this R21 application is to examine patterns of change in body habitus (weight, BMI, %body fat, waist circumference, fat mass, and fat-free mass) determined by objective laboratory assessments and in physical activity by using data from self-reported questionnaires as well as from maximal exercise tests as an objective laboratory marker of physical activity. We will apply sophisticated data analyses techniques to a large patient-oriented database which involved 12,199 free-living men and women 30 to 83 years who were enrolled in the Aerobics Center Longitudinal Study (ACLS). A distinguishing feature of the ACLS is the inclusion of a large number of patients with 3 or more clinical examinations that include standardized objective measures of maximal exercise tolerance, body habitus, and an extensive follow-up for morbid and mortal endpoints. Results from the ACLS are cited frequently in the scientific literature and have been influential in the development of recent national guidelines for physical activity. This study will address a critical public health challenge by markedly expanding our knowledge of the patterns of change in weight and activity during adulthood. Knowledge is needed to refine public health and clinical recommendations for healthful lifestyles. SPECIFIC AIMS will include 1) Describe the pattern of change in body habitus, physical activity habits, and cardiorespiratory fitness levels during adulthood;and evaluate the interrelationships of these exposures;2) Determine the associations of the pattern of changes in body habitus, physical activity, and cardiorespiratory fitness during adulthood with subsequent diabetes, other obesity-related cardiometabolic disorders, and mortality;3) Determine whether key variables such as dieting behavior, psychosocial factors, quality of life, and the timing and presence of clinically manifest disease influence the above relationships.