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KRAUS, W. E., C. E. TORGAN, B. D. DUSCHA, J. NORRIS, S. A. BROWN, F. R. COBB, C. W. BALES, B. H. ANNEX, G. P. SAMSA, J. A. HOUMARD, and C. A. SLENTZ. Studies of a targeted risk reduction intervention through defined exercise (STRRIDE). Med. Sci. Sports Exerc., Vol. 33, No. 10, 2001, pp. 1774–1784. Purpose: The Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) trial is a randomized controlled clinical trial designed to study the effects of exercise training regimens differing in dose (kcal·wk−1) and/or intensity (relative to peak VO2) on established cardiovascular risk factors and to investigate the peripheral biologic mechanisms through which chronic physical activity alters carbohydrate and lipid metabolism to result in improvements in these parameters of cardiovascular risk in humans. Methods: We will recruit 384 subjects and randomly assign them to one of three exercise training regimens or to a sedentary control group. The recruiting goal is to attain a subject population that is 50% female and 30% ethnic minority. The overall strategy is to use graded exercise training regimens in moderately overweight subjects with impairments in insulin action and mild to moderate lipid abnormalities to investigate whether there are dose or intensity effects and whether adaptations in skeletal muscle (fiber type, metabolic capacity, and/or capillary surface area) account for improvements in insulin action and parameters of lipoprotein metabolism. We will study these variables before and after exercise training, and over the course of a 2-wk detraining period. The study sample size is chosen to power the study to examine differences in responses between subjects of different gender and ethnicity to exercise training with respect to the least sensitive parameter—skeletal muscle capillary density. Results: The driving hypothesis is that improvements in cardiovascular risk parameters derived from habitual exercise are primarily mediated through adaptations occurring in skeletal muscle. Conclusion: Identification that amount and intensity of exercise matter for achieving general and specific health benefits and a better understanding of the peripheral mechanisms mediating the responses in carbohydrate and lipid metabolism to chronic physical activity will lead to better informed recommendations for those undertaking an exercise program to improve cardiovascular risk.