Some voluntary drive reaches human upper limb muscles via cervical propriospinal premotoneurones. Stimulation of the superficial radial nerve can inhibit these premotoneurones selectively and the resultant suppression of voluntary drive to motoneurones changes on-going electromyographic (EMG) activity. We investigated whether muscle fatigue changes this cutaneous-induced suppression of propriospinal drive to motoneurones of upper limb muscles. EMG was recorded from the extensors and flexors of the wrist and elbow. In the first study (n = 10 subjects), single stimuli (2 x perception threshold; 2PT) to the superficial radial nerve were delivered during contraction of the wrist extensors, before and after sustained fatiguing contractions of wrist extensors. In the second study (n = 10), similar stimuli were applied during elbow extension, before and during fatigue of elbow extensors. In the final study (n = 10), trains of three stimuli (2PT) were delivered during contractions of wrist extensors, before and while they were fatigued. With fatigue of either the wrist or elbow extensors, EMG suppression to single cutaneous stimuli increased significantly (by ~75%) for the fatigued muscle (P < 0.05). Conversely, in the other muscles, which were co activated but not principally involved in the task, inhibition decreased or facilitation increased. Trains of stimuli produced greater suppression of on-going wrist extensor EMG than single stimuli and this difference persisted with fatigue. A control study of the H reflex in extensor carpi radialis showed that the mechanism responsible for the altered EMG suppression in fatigue was not at a motoneurone level. The findings suggest that the proportion of descending drive mediated via the disynaptic propriospinal pathway or the excitability of inhibitory interneurones projecting to propriospinal neurones increases substantially to fatigued muscles, but decreases to other active muscles. This pattern of changes may maintain coordination during multi-muscle movements when one group of muscles is fatigued.