The central processes occurring during fatiguing exercise are not well understood, however transcranial magnetic stimulation (TMS) studies have reported increases both in corticomotor excitability, as measured by the motor-evoked potential (MEP) amplitude, and in long-interval intracortical inhibition, as measured by the duration of the post-MEP silent period. To determine whether short-interval cortical inhibition (SICI) is modulated by fatiguing exercise, we used single and paired-pulse TMS to measure MEP amplitude and SICI for the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles of the hand during, and for 20 min after, a 10-min intermittent maximal voluntary abduction of the index finger designed to fatigue the FDI muscle. For the FDI, the index of SICI increased at the onset of exercise (from 0.25 +/- 0.05 to 0.55 +/- 0.11, P < 0.05) and then decreased progressively as force declined. At the beginning of recovery, SICI again increased (0.57 +/- 0.11, P < 0.05) and remained elevated for the 20-min recovery period. In contrast, SICI for ADM did not change during or after exercise. MEP amplitude for both the FDI and ADM increased above baseline during exercise and then decreased below baseline during the recovery period. These results demonstrate that there are significant changes in SICI during and after a fatiguing exercise protocol that are isolated to the representation of the fatigued muscle. The inter-relationship between the changes in excitation and inhibition suggests the presence of a measured and adaptive process of modulation in central excitation and inhibition acting to increase corticomotor drive to the exercising muscle as fatigue is developing.