The malleability of muscle mass in response to neuromuscular activity, nutritional states and the general effects of illnesses, such as, cancer and AIDS are well recognized. further, since changes in muscle mass are largely due to the changes in the total cross sectional area of all muscle fibers in a muscle, i.e. the physiological cross sectional area, and since this measure is directly and very closely correlated with the force potential of the muscle, a clear understanding of the mechanism of control of cross sectional area of muscle fibers is of major importance. This becomes more important in individuals in which muscle atrophy has progressed to the point that fine or even gross motor control is so hampered as to affect daily tasks, such as, eating, general mobility and the capacity to move safely. Knowledge of how muscle size is regulated during adaptation will provide crucial information necessary to identify appropriate nursing interventions that will aid the process of recovery. The present proposal is designed to address this fundamental problem, i.e. how is the volume or cross sectional area of a muscle fiber regulated. Since there is a range of cross sectional areas among fibers within a muscle even after months of sustained electrical silence and in markedly hypertrophied muscle, factors specific to single fibers seem to contribute significantly to the regulation of fiber cross sectional area. this conclusion is further supported by studies which have shown a 30-40% coefficient of variation in size among fibers of a single motor unit. Further evidence shows that predictable relationships persist between fiber size, myosin type, and mitochondrial density. These findings lead to the hypothesis which will be tested in the proposed experiments: that the size of a muscle fiber is determined by the total number of myonuclei in a fiber, the type of myosin expressed and the mitochondria concentration. We will use confocal microscopy together with computer-aided analysis and visualization to quantify the number and spatial distributions of myonuclei, and to determine whether and how these features change when the muscle fiber changes myosin type and/or volume as a result of normal development, reduced use (when some slow fibers become fast and cell volume decreases), compensatory hypertrophy (when cell volume increases and some fast fibers become slow), and ectopic innervation in which doubly innervated fibers demonstrate both fast and slow subregions.