Previously, we showed that forearm venous congestion augmented muscle sympathetic nerve activity (MSNA) during static exercise. We postulated that venous congestion increased interstitial pressure, sensitizing mechanoreceptor afferents that led to a greater sympathoexcitation during exercise. In this study, we tested the hypothesis that forearm compression (FC) would increase interstitial pressure and selectively stimulate mechanically sensitive afferents. We measured MSNA during 2 min of ischemic static exercise (40% maximal voluntary contraction) and 2 min of posthandgrip circulatory arrest. Exercise was performed again after 5 min of FC induced by inflation of a forearm cuff to 90 mmHg (n = 6) and 110 mmHg (n = 7). FC without exercise had no effect on any of the hemodynamic variables. MSNA and mean arterial blood pressure responses were not augmented when exercise was performed with FC at 90 mmHg. However, static exercise coupled with FC at 110 mmHg did augment the reflex responses to static exercise (changes in MSNA before and after FC were 277 +/- 58 and 503 +/- 82 arbitrary units, respectively, P < 0.02; changes in mean arterial pressure before and after FC were 35 +/- 4 and 41 +/- 5 mmHg, respectively, P < 0.003). These responses were probably not due to greater metaboreceptor stimulation, since posthandgrip circulatory arrest responses were unaffected by FC. We postulate that FC sensitizes mechanoreceptors, leading to greater sympathoexcitation during exercise.