Muscle fatigue in McArdle's disease. Muscle fibre conduction velocity and surface EMG frequency spectrum during ischaemic exercise. The origin of fatigue in McArdle's disease is still a matter of debate. Both a reduction of muscle membrane excitability and failure of excitation-contraction (E-C) coupling have been suggested as causes. We performed intermittent isometric biceps brachii contractions (80% maximal voluntary contraction, rate 30/min) under local ischaemia in 5 McArdle's disease patients and 26 healthy controls. Our results show that in McArdle's disease the exerted force is less, the surface EMG (SEMG) amplitude steadily increases, and that the power density spectrum (PDS) shifts to lower frequencies, the latter without significant differences when compared with normals. The most important finding is that muscle membrane excitability remains unimpaired during ischaemic exercise, establishing a dominant role for intramuscular lactic acid formation in the reduction of muscle fibre conduction velocity seen in normal subjects. As is indicated by the shift of the PDS towards lower frequencies, as well as by the increase in SEMG amplitude, it can be concluded that during ischaemic exercise in patients with myophosphorylase deficiency, fatigue occurs without alterations in muscle membrane excitability and is due to a failure of E-C coupling. 