There are major spinal changes induced by repetitive activity and fatigue that could contribute to ‘central’ fatigue but the mechanisms involved are poorly understood in humans. Here we confirmed that the recurrent motoneuronal discharge (F-wave) is reduced during relaxation immediately after a sustained maximal voluntary contraction (MVC) of an intrinsic hand muscle (abductor digiti minimi, ADM) and explored the relationship between motoneurone firing and the depression of F-waves in three ways. First, the depression (in both F-wave area and F-wave persistence) was present after a 10 s MVC (initial decrease 36.4 ± 19.1%; mean ± SD) but not after a submaximal voluntary contraction at 50% maximum. Second, to evoke motoneurone discharge without volitional effort, 10 s tetanic contractions were produced by supramaximal ulnar nerve stimulation at the elbow at physiological frequencies of 25 and 40 Hz. Surprisingly, neither produced depression of F-waves in ADM to test supramaximal stimulation of the ulnar nerve at the wrist. Finally, a sustained MVC (3 min) of the antagonist to ADM (4th palmar interosseous) depressed F-waves in the anatomically close ADM (20 ± 18.2%) but not in the more remote first dorsal interosseous on the radial side of the hand. We argue that depression of F-waves after voluntary contractions may not be due to repetitive activation of the motoneurones but requires descending voluntary drive. Furthermore, this effect may depress nearby, but not distant, spinal motoneurone pools and it reveals potentially novel mechanisms controlling the output of human motoneurones.