This study investigates the relationship between systemic blood pressure, force output and fatigue in the human adductor pollicis muscle, a hand muscle in which fatigue-resistant oxidative fibres predominate, and the tibialis anterior muscle, which contains predominantly fatigue-prone gylcolytic fibres. Previously, we showed that as the local perfusion pressure of the contracting adductor pollicis declines within the physiological range, its force output is reduced [1] and it fatigues faster [2]. Systemic blood pressure (BP) increases when a muscle is voluntarily contracted and continues to increase as the muscle fatigues [2]. Here we investigate how that increase in systemic BP affects muscle performance. Subjects (N=6, 27-55 years) sat with the hand at heart level while supramaximal stimulation of the ulnar nerve produced repeated (1 Hz) tetanic contractions (5 at 40 ms) of adductor pollicis. Isometric force output gradually declined indicating a progressive muscle fatigue. After 2 min of these contractions force had declined by an average of 15%. We then raised BP by having subjects make a sustained isometric voluntary contraction of a thigh muscle. As systemic BP rose (29 ± 2.9 mmHg; mean ± S.E.M.), force output from adductor pollicis increased to recover 39 ± 5.8% of the lost force. When the leg contraction was stopped and systemic BP fell back to normal levels, force output from the hand muscle again fell gradually. Control experiments in which local perfusion pressure in the hand was kept constant despite the increase in systemic blood pressure confirmed that the increased force output was a consequence of the greater systemic BP and not corollary neural drive to the muscle. The electrical stimulation of adductor pollicis by itself did not cause systemic blood pressure to rise. Equivalent findings were observed in 3 subjects when tibialis anterior was electrically stimulated at its motor point and systemic blood pressure was increased by a voluntary contraction of adductor pollicis. These results do not support the notion that autoregulation of muscle blood flow maintains muscle performance across the physiological range of blood pressures. The increase in systemic blood pressure that is produced as a corollary of the voluntary contraction of a muscle improves muscle performance, offsetting but not cancelling the fatigue-related decline in muscle performance. This behaves as if sensory information about muscle performance serves as the feedback ‘signal’ that controls the extent of the blood pressure rise during muscular work. Our results suggest that working muscles would fatigue approximately twice as fast without this feedback control.