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Background: Exercise interventions elicit only modest weight loss, which might reflect a compensatory reduction in nonprescribed physical activity energy expenditure (PAEE). Objective: The objective was to investigate whether there is a reduction in nonprescribed PAEE as a result of participation in a 6-mo structured exercise intervention in middle-aged men. Design: Sedentary male participants [age: 54 [+ or -] 5 y; body mass index (in kg/[m.sup.2]): 28 [+ or -] 3] were randomly assigned to a 6-mo progressive exercise (EX) or control (CON) group. Energy expenditure during structured exercise (prescribed PAEE) and nonprescribed PAEE were determined with the use of synchronized accelerometry and heart rate before the intervention, during the intervention (2, 9, and 18 wk), and within a 2-wk period of detraining after the intervention. Results: Structured prescribed exercise increased total PAEE and had no detrimental effect on nonprescribed PAEE. Indeed, there was a trend for greater nonprescribed PAEE in the EX group (P = 0.09). Weight loss in the EX group (- 1.8 [+ or -] 2.2 kg compared with +0.2 [+ or -] 2.2 kg in the CON group, P < 0.02) reflected only ~40% of the 300-373 kcal/kg body mass potential energy deficit from prescribed exercise. Serum leptin concentration decreased by 24% in the EX group (compared with 3% in the CON group, P < 0.03), and we estimate that this was accompanied by a compensatory increase in energy intake of ~100 kcal/d. Conclusions: The adoption of regular structured exercise in previously sedentary, middle-aged, and overweight men does not result in a negative compensatory reduction in nonprescribed physical activity. The less-than-predicted weight loss is likely to reflect a compensatory increase in energy intake in response to a perceived state of relative energy insufficiency. doi: 10.3945/ajcn.2010.29471