We questioned if a non-linear increase in ventilation defining a ventilatory threshold (V(Th)) accompanied the electromyographic (EMG) signs of neuromuscular fatigue. Indeed, the intramuscular accumulation of metabolites may activate the afferent nervous pathways responsible for both the 'muscle wisdom' phenomenon and the respiratory centre activation. During inframaximal (50%) handgrip sustained until exhaustion, minute ventilation (V(E)), V(E)/V(O2) and V(E)/V(CO2) ratios were measured simultaneously with surface EMG of the 'flexor digitorum' muscle. V(Th) was defined as a non-linear V(E) increase and/or an abrupt V(E)/V(O2) increase without any concomitant increase in the V(E)/V(CO2) ratio. Handgrip was repeated during complete arterial blood flow interruption in order to suppress any venous return from the exercising forearm. In both control and blood flow interruption conditions, an abrupt increase in the V(E)/V(O2) ratio was measured in the majority of trials (13 of 15 and 14 of 15, respectively) and the EMG signs of neuromuscular fatigue (a decline in median frequency and/or a non-linear increase in low-frequency EMG energies, E(L)) were concomitant with the V(Th) determination. Thus, V(Th) occurs during sustained static contraction and is concomitant with EMG signs of neuromuscular fatigue. Neurogenic factors seem to be responsible for the two responses which persist despite the absence of any release of metabolites in the circulation.