The responses to magnetic brain stimulation of 57 motor units (MUs) in the first dorsal interosseous muscle of 33 patients with sporadic motor neuron disease (MND), and 44 MUs of 15 healthy control subjects have been compared. Thresholds for MU excitation both in the resting state and during tonic activity have been measured and the modulation of MU discharge by series of magnetic stimuli has been determined from peristimulus time histograms (PSTHs). Abnormalities in the MND MUs have been correlated with the physical signs of impaired hand muscle function. Motor units from hands showing pure lower motor neuron (LMN) signs fired at increased frequency when recruited, had normal or reduced thresholds for activation by magnetic scalp stimuli and had normal or large primary excitatory peaks with normal inter-subpeak intervals on PSTHs. Occasionally muscles with pure LMN signs also had fasciculations that could be driven by cortical stimuli. In contrast, MUs from hands showing pure upper motor neuron (UMN) signs fired at reduced frequency when recruited, had raised thresholds for excitation by cortical stimuli, had prolonged primary peaks with wide inter-subpeak intervals and had large secondary peaks on PSTHs. The rise times and amplitudes of the underlying post-synaptic potentials released by cortical stimuli in spinal motor neurons have been deduced from measurements of the peaks in PSTHs. This analysis suggests that in some MUs from muscles showing pure LMN signs, stimuli evoke larger than normal excitatory post-synaptic potentials (EPSPs), probably resulting from abnormalities in central motor fibres. It is proposed that a major cause of the changes found in MND MUs from hands showing either pure UMN or pure LMN signs may be an abnormality in the motor cortex leading to faulty initiation of the descending corticospinal volley from magnetic stimuli.