Abstract Objectives Previous studies have revealed a selective functional loss of the large, high-threshold motor units in the paretic muscles after lesion of the upper motor neuron. We set out to study the degree and the time course of the reorganization of the motor units following a stroke. Methods Examinations were performed on 59 patients with a unilateral ischemic stroke in the territory of the middle cerebral artery, and on 42 healthy controls. The duration of hemiparesis ranged from 2 weeks to 48 months. The fiber density (FD) in the abductor digiti minimi muscle was determined by means of single-fiber electromyography on both the hemiparetic and the unaffected side in the patients, and unilaterally in the control subjects. Results The FD was increased on the hemiparetic side relative to the unaffected side and the control group. This change correlated with the severity of the clinical signs. The FD increased during the first 10 months following the stroke and subsequently remained stable. Conclusions The process of reinnervation in the muscles takes place in the acute phase after stroke. These changes are related to the severity of the symptoms. Significance Our findings suggest that trans-synaptic degeneration of the spinal motor neurons occurs shortly after the lesion of the upper motor neurons.