Exercise-induced increases in skin sympathetic nerve activity (SSNA) are similar between isometric handgrip (IHG) and leg extension (IKE) performed at 30% of maximal voluntary contraction (MVC). However, it is unclear is the precise effect of exercise intensity and level of fatigue on this relationship. This study tested the following hypotheses: 1) exercise intensity and fatigue level would not affect the magnitude of exercise-induced increase in SSNA between IHG and IKE, and 2) altering IHG muscle mass would also not affect the magnitude of exercise-induced increase in SSNA. Protocol 1: SSNA (peroneal microneurography) was measured during baseline, and during the initial and last 30 sec of isometric exercise to volitional fatigue in 12 subjects who randomly performed IHG and IKE bouts at 15, 30, and 45% MVC. Protocol 2: SSNA was measured in 8 subjects who performed 1-arm IHG at 30% MVC with the addition of IHG of the contralateral arm in 10 sec intervals for 1 min. Exercise intensity significantly increased SSNA responses during the first 30 sec of IHG (34±13, 70±11, and 92±13% change from baseline) and IKE (30±17, 69±12, and 76±13% change from baseline) for 15, 30, and 45% MVC. During the last 30 sec of exercise to volitional fatigue, there were no significant differences in SSNA between exercise intensities or limb. SSNA did not significantly change between 1-arm to 2-arm IHG. Combined, these data indicate that exercise-induced increases in SSNA are intensity dependent in the initial portion of isometric exercise but these differences are eliminated with the development of fatigue. Moreover, the magnitude of exercise-induced increase in SSNA responses is dependent neither on muscle mass involved nor exercising limb.