Rats, monkeys, and humans can alter the size of their spinal stretch reflex and its electrically induced analog, the H-reflex (HR), when exposed to an operant conditioning paradigm. Because this conditioning induces plasticity in the spinal cord, it offers a unique opportunity to identify the neuronal sites and mechanisms that underlie a well-defined change in a simple behavior. To facilitate these studies, we developed an HR operant conditioning protocol in mice, which are better suited to genetic manipulation and electrophysiological spinal cord study in vitro than are rats or primates. Eleven mice were implanted with tibial nerve stimulating electrodes and soleus and gastrocnemius intramuscular electrodes for recording ongoing and stimulus-evoked electromyographic activity (EMG). During the 24-hr/day computer-controlled experiment, mice received a liquid reward for either increasing (up-conditioning) or decreasing (down-conditioning) HR amplitude, while maintaining target levels of ongoing EMG and directly evoked EMG (M-responses). After 3-7 weeks of conditioning, the HR amplitude±SE was 133±7% of control for up-conditioning and 71±8% of control for down-conditioning. HR conditioning was successful (i.e., >20% change in HR amplitude in the appropriate direction) in 5 of 6 up-conditioned animals (final HR amplitude±SE=139±5% of control HR for successful mice) and in 4 of 5 down-conditioned animals (final HR amplitude±SE=63±8% of control HR for successful mice). These effects were not attributable to differences in the net level of motoneuron pool excitation, stimulation strength, or distribution of HR trials throughout the day. Thus, mice exhibit HR operant conditioning comparable to that observed in rats and monkeys.