A previous study in our laboratory showed a long-lasting, naloxone-reversible inhibition of the flexion reflex after prolonged repetitive stimulation of a peripheral nerve in the spinal cat. The present study employed a special pattern of conditioning stimulation for a shorter period (200 s) to determine the time course of the inhibition and the afferent fibers responsible for the inhibition. We stimulated the common peroneal nerve in 10 decerebrated and spinalized cats to elicit the flexion reflex, which we recorded as single-unit activity from filaments of the L7 ventral root. The C fiber-evoked late component of the flexion reflex was compared before, during, and after conditioning electrical stimulation applied to the tibial nerve. Stimulating the tibial nerve at an intensity that excited only A alpha beta fibers produced weak inhibition of the flexion reflex; increasing intensity above the threshold for A delta fibers produced much greater inhibition. Inhibition began during the first 10 s of conditioning stimulation and was maximum at about 100 s. Stimulation at a suprathreshold intensity for C fibers, however, produced an initial transient excitation, lasting 10 to 20 s, followed by inhibition. Intravenous injection of naloxone (0.05 mg/kg) produced no observable changes in this inhibition and excitation. These results suggest that conditioning stimulation of a peripheral nerve inhibits the flexion reflex. This inhibition has a short latency; the afferent fibers seem to be A delta fibers. In addition, input from afferent C fibers may trigger a mechanism that produces facilitation of the reflex. The differences in recovery time course and in sensitivity to naloxone suggest that two different mechanisms may be responsible for the fast-onset inhibition and the previously observed long-lasting inhibition produced after prolonged conditioning stimulation.