Learning to perform a motor task with one hand results in performance improvements in the other hand, a process called intermanual transfer. To gain information on its neural mechanisms, we studied this phenomenon using the serial reaction-time task (SRTT). Sixteen, right-handed volunteers trained a 12-item sequence of key presses repeated without the subjects' knowledge. Blocks with no repeating sequence, called random blocks, were interspersed with sequence-training blocks. Response times improved in random and training blocks in both hands. The former result reflects nonspecific improvement in performance, and the latter represents a sequence-specific improvement. To evaluate changes in the primary motor cortex (M1), we tested resting motor thresholds (RMT), recruitments curves to transcranial magnetic stimulation (RC), short intracortical inhibition (SICI), and interhemispheric inhibition (IHI) from the dominant left (learning) to the nondominant right (transfer) hemisphere, before and after SRTT training. Training resulted in (1) increased RC and decreased SICI but no changes in RMT in the learning hemisphere, (2) decreased SICI and no changes in RC or RMT in the transfer hemisphere, and (3) decreased IHI. The amount in IHI after training correlated with nonspecific performance improvements in the transfer hand but not with sequence-specific performance improvements. Our results indicate that modulation of interhemispheric inhibition between the M1 areas may, as a result of the learning that has occurred in one hemisphere after practice with one hand, contribute to faster, more skilled performance of the opposite hand.