Increased activity of muscle metaboreceptors (afferents sensitive to muscle contraction that are responsible for the ventilatory responses to exercise) has been proposed in patients with chronic heart failure (CHF) to constitute a missing link between muscle metabolic abnormalities and exercise overventilation. We looked at this reflex overactivation to determine if it is systemic or limited to a single muscle region in the same human subject. This was done by comparing the metaboreflex response of ventilatory control in the lower and upper limbs in CHF patients and healthy controls. Groups of 15 stable CHF patients (63.7+/-2.7 years) and eight control subjects (69.8+/-1.8 years) performed both leg and arm metaboreflex tests. These metaboreflex tests involved two 5 min episodes of bicycle or handgrip exercise: on one occasion after the exercise the subjects recovered normally, while on the other occasion tourniquet cuffs were inflated around the exercising limb to supra-systolic pressure at the onset of recovery to obtain a regional circulatory occlusion, which isolates and maintains the stimulation of the metaboreflex after exercise. The contribution of the metaboreflex to exercise ventilation was computed as the absolute increment of peak ventilation that was maintained by regional circulatory occlusion. The metaboreceptor contribution to the ventilatory response to both leg exercise (patients, 5.3+/-1.6 litres/min; controls, 0.2+/-0.7 litres/min) and arm exercise (patients, 3.7+/-1.0 litres/min; controls, 0.02+/-0.4 litres/min) was significantly higher in CHF patients (P<0.05). A significant correlation was present between metaboreflex responses to arm and leg exercises (r=0.4, P<0.05). Metaboreflex responses during both types of exercise were inversely correlated with peak oxygen uptake (leg, r=-0.43, P<0.05; arm, r=-0.633, P=0.0009), but only the reflex during arm exercise was correlated with the .V(E) (ventilation)/.V(CO)(2) (CO(2) production) slope (r=0.576, P<0.005). Thus the metaboreflex system is systemically overactive and may potentially contribute to exercise intolerance during both lower- and upper-limb efforts in CHF. This suggests a unique mechanism responsible for overactivation of this system in the skeletal muscle of heart failure patients.