The purpose of this study was to test the hypothesis that sympathetic vasoconstriction is rapidly blunted at the onset of forearm exercise. Nine healthy subjects performed 5 min of moderate dynamic forearm handgrip exercise during −60 mmHg lower body negative pressure (LBNP) vs. without (control). Beat-by-beat forearm blood flow (Doppler ultrasound), arterial blood pressure (finger photoplethysmograph), and heart rate were collected. LBNP elevated resting heart rate by ∼45%. Mean arterial blood pressure was not significantly changed ( P = 0.196), but diastolic blood pressure was elevated by ∼10% and pulse pressure was reduced by ∼20%. At rest, there was a 30% reduction in forearm vascular conductance (FVC) during LBNP ( P = 0.004). The initial rapid increase in FVC with exercise onset reached a plateau between 10 and 20 s of 126.6 ± 4.1 ml · min⁻¹ · 100 mmHg⁻¹ in control vs. only 101.6 ± 4.1 ml · min⁻¹ · 100 mmHg⁻¹ in LBNP (main effect of condition, P = 0.003). This difference was quickly abolished during the second, slower phase of adaptation in forearm vascular tone to steady state. These data are consistent with a rapid onset of functional sympatholysis, in which local substances released with the onset of muscle contractions impair sympathetic neural vasoconstrictor effectiveness.