INTRODUCTION & PURPOSE: A recent report suggests that periodic bouts of blood flow occlusion to skeletal muscle during surgically-induced bed rest results in atrophy attenuation (Takarada et al., 2000). To our knowledge this observation has not be re-investigated, nor is it known how applied ischemia (AI) affects other facets of muscle function. Therefore, the purpose of this study was to investigate the effect of AI on skeletal muscle function following 4-weeks of unilateral lower limb suspension (ULLS; an experimental model of disuse). METHODS: Measurements of voluntary and stimulated forces, the compound muscle fiber action potential (CMAP) and muscle cross-sectional area (CSA, via MRI) were collected before and after a 4-week control period and 4-weeks of ULLS in healthy adults (n=18; 19–28 years). A subset of these subjects (n=6) received AI 3 days per week (3-sets; 5-minutes duration) during the ULLS period. RESULTS: In subjects not receiving AI, the loss in muscle mass and strength was as expected (∼ 9 & 14%). We observed a 30% slowing in the duration of the CMAP, an altered force-frequency relation (12% increase in the twitch-to-doublet ratio), and post-activation potentiation force response (11% increase in the PAP-to-doublet ratio). We also detected a 10% slowing in the ability of the muscle to develop force during the initial, but not latter phase of an evoked contraction, along with a 6% reduction in in vivo specific force (doublet force/CSA). In the subjects receiving the AI, no mitigation was observed in muscle strength, nor did it alter the evoked force properties. We did, however, observe a preferential maintenance of the lateral gastrocnemius CSA in subjects using AI (control and AI atrophy: 10.2% vs. 4.7%, respectively) with no affect of AI on the solves, and a trend towards atrophy attenuation in the medial gastrocnemius. Additionally, AI abolished the un weighting-induced slowing in the CMAP. CONCLUSION:These findings suggest that AI impacts the sarcolemma and preferentially affects the type II muscle fibers, but does not influence the force generating capacity of the muscle. This work was supported in part by the following: NASA Training Grant (NGT5-50446), the 2004 and 2005 NASA Space Physiology Research Grant through the American College of Sports Medicine (ACSM) Foundation, and the 2003 ACSM Mid-Atlantic Regional Chapter Research Award.