It is not fully understood how the sympathetic nervous system controls blood flow to contracting skeletal muscle, and recent findings have indicated that there may be differential control between active and inactive muscle. Stimulation of metabolically sensitive receptors in skeletal muscle during exercise can activate the metaboreflex and is one such mechanism that has been demonstrated to influence muscle sympathetic nerve activity (MSNA) to non-contracting muscle. However, it is not clear whether it influences sympathetic outflow to contracting muscle. Similarly, mechanically sensitive receptors in skeletal muscle stimulate a mechanoreflex, which might also influence sympathetic responses to active muscle during exercise. Evidence also pertains to direct projections from the motor regions of the brain, referred to as central command, as another mechanism that could influence MSNA to contracting muscle. The aim of this thesis was to reveal the role of these particular central and peripheral mechanisms in the control of sympathetic activity to contracting muscle during exercise. To determine how MSNA to the vascular beds of active muscle is controlled during static (isometric) exercise a series of studies were conducted to identify the key mechanisms. In each study MSNA was recorded directly from a muscle fascicle of the common peroneal nerve in male subjects, via microneurography, to either a contracting or non-contracting leg. Force, muscle electromyography (EMG), arterial blood pressure, respiration and heart rate (ECG) were also measured continuously. vi In Study One the involvement of central command was explored by testing the hypothesis that the increase in MSNA to contracting muscle is greater during voluntary compared with electrically evoked contractions of the same force. MSNA was measured to the active leg while seven subjects performed a series of one-minute ankle dorsiflexions at 10 % maximum voluntary contraction (%MVC), alternating between voluntary and electrically evoked contractions separated by two-minute rest periods. MSNA was analysed in 15-second epochs and demonstrated a short delay of 15 – 30 seconds before increasing 51 } 34 % (32.5 } 5.9 vs 48.6 } 10.6 spikes/min, P < 0.01) during voluntary, but not electrically evoked (-8 } 12 %, 34.0 } 7.9 vs 31.3 } 5.6 spikes/min, P > 0.05), contractions. The elevation in MSNA during voluntary contractions was sustained during the contraction and decreased within 15 seconds after the contraction ceased, supporting the hypothesis and indicating that central command, and not the muscle mechanoreflex, is the primary mechanism responsible for the increase of MSNA to contracting muscle. In Study Two the role of the muscle metaboreflex in regulating MSNA during exercise was investigated by testing the hypothesis that sympathetic activity increases to non-contracting, but not contracting, muscle due to metaboreflex activation. Eleven subjects performed a series of prolonged ankle dorsiflexions ipsilateral and contralateral to the neural recording at 10 %MVC. Supra-systolic muscle ischaemia of the contracting limb was imposed at different stages of the protocol to determine if modulation of muscle metaboreflex activation affected the response of MSNA to active or inactive skeletal muscle during exercise. The following conditions were applied: (i) no ischaemia during and after exercise, (ii) vii muscle ischaemia after exercise only, and (iii) muscle ischaemia during and after exercise. MSNA responded differently to contractions ipsilateral and contralateral to the neural recording. Ipsilateral contractions exhibited a rapid 48 } 55 % increase (34 } 10 vs 50 } 18 spikes/min, no ischaemia, P = 0.01) of resting levels within the first minute of contraction, which plateaued until contraction ceased. A rapid offset response in MSNA to the contracting leg was also observed, decreasing to pre-contraction levels within one-minute of contraction ending even when muscle ischaemia was imposed. In contrast, MSNA during contralateral contractions remained at resting levels after one-minute of contraction (5 } 22 %, 32 } 5 vs 34 } 9 spikes/min, no ischaemia, P = 0.48). However, MSNA to the non-contracting limb increased 40 } 35 % (44 } 8 spikes/min, P = 0.01) of resting levels after two minutes of contraction, progressively increasing throughout the contraction and remained elevated during post-exercise ischaemia. Ischaemia augmented the exercise-induced response in MSNA to noncontracting (i.e. contralateral to contractions), but not contracting (i.e. ipsilateral to contractions), skeletal muscle. These results support the hypothesis and suggest that muscle metaboreflex activation in the active limb increases MSNA to non-contracting muscles only. In Study Three the hypothesis that muscle metaboreflex-mediated increases in MSNA to inactive muscle are greater during exercise of the upper than lower limb was tested to further investigate the role of the metaboreflex during sustained contractions. Eight subjects performed four-minute ischaemic ankle viii dorsiflexions of the leg contralateral to the neural recording and ischaemic handgrip of the same duration. Responses in MSNA were similar, with an incremental increase throughout contraction up to 100 % (33 } 7 vs 66 } 24 spikes/min, P < 0.01) and 103 % (31 } 8 vs 63 } 25 spikes/min, P < 0.01) of resting levels for handgrip and ankle dorsiflexion, respectively. These results indicate that muscle metaboreflex stimulation of MSNA is similar during lowintensity isometric exercise of different limbs. The control of sympathetic vasoconstrictor drive to muscle is complex and is influenced by many factors during exercise. Collectively, these studies indicate that MSNA to contracting muscle at low force is primarily controlled by central command, whereas MSNA to non-contracting muscle is controlled by the muscle metaboreflex. Sympathetic activity to skeletal muscle is important for the regulation of blood pressure and the control of blood flow during low-intensity exercise. It is important to note that these studies do not exclude the potential for other mechanisms to influence the MSNA response to exercise, particularly with respect to different forms of exercise.