To locate the exact site of the primary lesion in the neuromuscular system in acutely ischaemic extremities. Experimental study. University hospital, Greece. 22 adult rats. Isometric tensions of extensor digitorum longus muscles were recorded before ischaemia and every 5 minutes after the arterial occlusions by indirect stimulation. When no contractile activity was elicited, the muscle was stimulated directly and recordings made every 5 minutes. The sciatic nerve function was checked by recordings of nerve conduction velocity. Specimens from the muscles were examined under electron microscopy. Muscle contractile properties, conduction velocity, and electron microscopic appearance. After a period of about 50 minutes neuromuscular function under indirect stimulation in the ischaemic limbs was lost, whilst under direct stimulation the extensor digitorum longus muscles and the sciatic nerves still functioned. Electron microscopic study showed distinct alterations at the neuromuscular junctions. The response of the neuromuscular system to acute ischaemia indicated that the neuromuscular junction is probably the site most susceptible to acute ischaemia.