Prolonged changes in crayfish motoneuron electrical activity result in adaptations in neuromuscular synapses which are consistent with findings at other synapses. In this study we establish that this long-term adaptation (LTA) of crayfish neuromuscular synapses to increased activation of the motoneuron does not require the activation of any other neurons. Selectively increasing the impulse activity of the relatively inactive fast closer excitor motoneuron (FCE) over a period of 7 days results in a 41% reduction in initial amplitude of the excitatory postsynaptic potential (EPSP), and a 42% decrease in synaptic fatigue. These changes in EPSP properties have been previously shown to be due to decreased initial transmitter release and greater sustained release of transmitter during prolonged stimulation. Chronic stimulation of sensory receptors known to produce subthreshold synaptic potentials in the central processes of the FCE elicits LTA of its neuromuscular synapses. The initial EPSP is decreased by 21%, and the synaptic fatigue is reduced by 17%. These results lead to the hypothesis that the primary event leading to LTA of neuromuscular synapses is depolarization of the motoneuron.