Macro-EMG potentials (MEP)s and twitch contractions (spike-triggered-averaging) of single motor units (MUs) have been recorded in the first dorsal interosseus muscle (FDI) of 10 control subjects and 20 patients with amyotrophic lateral sclerosis (ALS). MUs over the full range of voluntary recruitment thresholds were studied. Patients with slightly affected FDIs (5) mainly showed MUs with enlarged MEPs and increased twitch forces. In contrast, the patients with more severely affected FDIs (15) revealed decreased twitch forces, especially in the MUs with higher thresholds. The corresponding MEPs could be enlarged as well as normal. It appears that MU sprouting and the resulting increase of twitch force can compensate for the loss of motoneuron in early stages of ALS. In more advanced stages, however, a decline of the force of the surviving MUs, especially of those with higher thresholds, seems to contribute to the progressive muscle weakness, in addition to the corticospinal degeneration and the reduction in the number of motoneurons.