Non-technical summary Clonidine, a noradrenaline-like drug, facilitates the recovery of hindlimb walking in adult cats following a complete spinal cord injury.We show that clonidine improves operation of reflex pathways that coordinate bilateral hindlimb activity in cats after spinal cord injury. In addition, sensory signals from the periphery more easily activate the spinal network involved in producing locomotion following clonidine injection.These results show that spinal neurons that produce locomotion and coordinate bilateral activity become more excitable with clonidine.These data could help identify neurons of the spinal locomotor network and lead to a better pharmacotherapy in spinal cord-injured humans.Abstract Clonidine, an α-noradrenergic agonist, facilitates hindlimb locomotor recovery after complete spinal transection (i.e. spinalization) in adult cats. However, the mechanisms involved in clonidine-induced functional recovery are poorly understood. Sensory feedback from the legs is critical for hindlimb locomotor recovery in spinalized mammals and clonidine could alter how spinal neurons respond to peripheral inputs in adult spinalized cats. To test this hypothesis we evaluated the effect of clonidine on the responses of hindlimb muscles, primarily in the left hindlimb, evoked by stretching the left triceps surae muscles and by stimulating the right tibial and superficial peroneal nerves in eight adult decerebrate cats that were spinalized 1 month before the terminal experiment. Cats were not trained following spinalization. Clonidine had no consistent effect on responses of ipsilateral muscles evoked by triceps surae muscle stretch. However, clonidine consistently potentiated the amplitude and duration of crossed extensor responses. Moreover, following clonidine injection, stretch and tibial nerve stimulation triggered episodes of locomotor-like activity in approximately one-third of trials. Differential effects of clonidine on crossed reflexes and on ipsilateral responses to muscle stretch indicate an action at a pre-motoneuronal site. We conclude that clonidine facilitates hindlimb locomotor recovery following spinalization in untrained cats by enhancing the excitability of central pattern generating spinal neurons that also participate in crossed extensor reflex transmission.