Acetylcholine was shown to maintain the efficiency of a fatigued muscle of rat increasing the evoked transmitter release and inducing a hyperpolarization of the muscle fibre membrane. The effects proved to be long-term ones. Modulatory effects of acetylcholine were shown to be realized via structures which differed pharmacologically from the typical n- and m-cholinoreceptors with the participation of ouabain-sensitive isoforms of Na+, K(+)-ATPase. The data obtained corroborates existence of a long-term neuronal regulation of the neuromuscular transmission efficiency involving non-quantal acetylcholine. The regulatory pathways are supposed to be different in muscle fibres with different functional characteristics and different ability of adaptation under physiological loading.