Intrinsic spinal networks control much of the rhythmic motor neuron activity that underlies locomotion. These spinal rhythm-generating networks are known as central pattern generators (CPGs), and are thought to function as local command and control centres for the phasic activation of motor neurons during locomotion in all vertebrates, including man. The precise organization of the mammalian CPG is, however, so far unknown. In this talk I will review findings that have identified CPG neurons involved in the left-right alternation during locomotion. These neurons play and important role in coordinating flexor and extensor activity between the two sides of the body. I will also review findings showing that knockout of the axon guidance molecule EphA4 results in an abnormal hopping gait in mice. These dramatic changes in gaits are due to a genetic reconfiguration of the CPG, which can be explained by aberrant crossing of excitatory CPG interneurons in mutants. I will furthermore review data that have shown that many interneurons expressing EphA4 in lumbar spinal cord are rhythmically active during locomotion. A subset of these neurons provide monosynaptic excitation of motor neurons on the same side defining them as being involved in generating the local ipsilateral rhythmic motor activity. A large number of EphA4-positive interneurons are derived from the V2 interneuron population defined by expression of Chx10 in the embryonic spinal cord. These results suggest that that the axon guidance molecule EphA4 in combination with the transcription factor Chx10 defines a population of ipsilateral locomotor-related interneurons.