The pattern of upper-limb muscle activation following painful stimulation has not been clarified in detail. We investigated the short-term inhibitory and excitatory effects of painful electrical digital stimulation on the motoneuron pools of distal and proximal upper-limb muscles. Transcranial magnetic stimulation (TMS) was used as test stimulus, and painful digital nerve stimulation as conditioning stimulus for motor evoked potential (MEP) recordings over the abductor digiti minimi (ADM), abductor pollicis brevis (APB), biceps brachii (BB), and deltoid muscles. Inhibition of the conditioned MEP response was most prominent in the distal muscles, whereas BB and deltoid muscles were only weakly inhibited. The mean MEP response over APB decreased with painful cutaneous stimuli, showing maximum inhibition (by 82%) at interstimulus intervals (ISIs) of 50 ms. Inhibition in the ADM was maximal (49%) but less pronounced at an ISI of 40 ms. The BB and deltoid muscles showed inhibition by 25% and 29%, respectively. Significant facilitation was present in BB and deltoid muscles by 43% and 41% at an ISI of 100 ms, but not in the smaller hand muscles. The observed pattern of upper-limb muscle activation corresponds to the protective withdrawal reflex and the neuronal basis of the observed short-term modulation of motor activity is compatible with a spinal or brainstem pathway.