Data from studies of elbow-flexor (EF) or knee-extensor (KE) muscles suggest that a fatigue-related decrease in motoneuron excitability only occurs in EF. It is unknown how motoneuron excitability changes after sustained fatiguing maximal voluntary isometric contractions (MVICs) in EF and KE in the same participants. In two sessions, eight healthy men performed a 2-min MVIC of EF or KE to induce fatigue with brief MVICs before and six times after the 2-min MVIC. Electromyographic responses elicited by corticospinal tract stimulation at the transmastoid [cervicomedullary motor-evoked potential (CMEP)] or thoracic [thoracic motor-evoked potential (TMEP)] level were recorded from EF and KE, respectively. To account for muscle excitability, CMEPs and TMEPs were normalized to maximal M-wave (Mmax) elicited by peripheral nerve stimulation during each brief MVIC. Immediately after the 2-min MVIC, biceps brachii and brachioradialis CMEP/Mmax were 88% (SD 11%) (P = 0.026) and 87% (SD 12%) (P = 0.029) of pre-MVIC values, respectively, and remained lower than PRE after 5 s of recovery [91% (SD 8%), P = 0.036 and 87% (SD 13%), P = 0.046, respectively]. No subsequent time points differed from PRE (all P ³ 0.253). TMEP/Mmax for rectus femoris and vastus lateralis were not different from PRE at any time during the recovery period (all P > 0.050). A different recovery pattern in motoneuron excitability occurred in EF as it recovered by 60 s whereas KE motoneurons were unaffected by the fatiguing task. The present findings may contribute to better understand muscle-specific neurophysiological differences in spinal excitability.