An isolated segment of the spinal cord, when its sensory and motor peripheral mechanisms are preserved intact, is capable of acquiring substitute responses (i.e., of establishing new sensori-motor connections) which were not reflexively present after transection. Mechanical or electric stimulation of the tail is combined with shock to a hind paw until M. semitendinosus responds when the tail alone is stimulated. The mechanisms of conditioning and extinction appear to be similar if not identical synaptic processes, since conditioning and extinction curves are shown to be superposable and reconditioning and reextinction occur more readily with each repetition. Central conditioning is differentiated from peripheral motor conditioning and central extinction from failure of the peripheral conditioned response. The mechanisms of conditioning and extinction are made available for psychological and physiological analysis as specific, cumulative, synaptic steady states. Evidence from delimited spinal roots indicates that the central conditioning process is located at the level of the spinal cord at which the conditioned muscle response is innervated.