The spinal cord of the lamprey, a primitive vertebrate, has been used as a model system for investigating the cellular basis of rhythmic locomotor activity. Three classes of interneurons have been characterized that are active during locomotor activity in the isolated spinal cord (ie fictive swimming). The identified synaptic interactions of these neurons form a network which has been proposed to underlie locomotor rhythmogenesis. Modeling studies confirmed that the network can produce oscillatory activity with phase relations among the neurons similar to those found in the spinal cord. Within the network, inhibitory commissural interneurons form reciprocal inhibitory connections and play a key role in rhythmogenesis. Several experiments have been done to test whether these cells participate in the generation of rhythmic activity in the spinal cord. First, midline lesions that sever the axons of commissural interneurons eliminate rhythmic ventral root bursting. Second, photo-ablation of commissural interneurons on one side of the spinal cord alters the symmetry of ventral root bursts, alters the cycle period, and can eliminate rhythmic bursting. Taken together, these experiments support the model that commissural interneurons are involved in rhythmogenesis in the lamprey spinal cord.