The numbers and relative sizes of motor units have been estimated in 373 muscles of 123 patients with ALS: 74 of the muscles were examined on more than one occasion. The median duration between the onset of symptoms and the initial examination was 12 months; by this time, approximately 90% of the tested muscles showed losses of motor units. The evoked motor unit potentials continued to enlarge in most, but not all, muscles as the disease progressed. Once a muscle became affected by the disease process, the average time-course was such that the motor unit population halved in each 6-month period of the first year and diminished more slowly thereafter. A small proportion of patients was encountered in whom the disease progressed much more slowly and there were occasional large fluctuations in the motor unit estimates suggestive of reversible motoneuron dysfunction.