Monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded from the triceps surae motoneurons in the rat. Two to 3 weeks after section of the medial gastrocnemius (MG) nerve, Ia EPSPs evoked by stimulation of the MG nerve were significantly depressed, as reported previously. However, the MG EPSP amplitude significantly increased within 24 h, reaching a maximum on the 3rd day after axotomy. This increase was prevented by actinomycin-D treatment, indicating that the synaptic enhancement is dependent upon protein synthesis. When disuse of sensory fibers was induced without injuring the muscle nerve, the degree of synaptic enhancement was similar to that after axotomy. Therefore, the enhancement of central synaptic transmission shortly after axotomy is due to the loss of electrical activity, but not due to the axon reaction of the Ia sensory neurons to injury. It is postulated that the presence of some factor in Ia sensory fibers enhances synaptic transmission, while electrical activity of the neurons antagonizes the action of this factor.