This report concerns an ultrastructural examination of the synapses present on the surface of somata of anterior horn neurons of the lumbar spinal cord of seven patients with amyotrophic lateral sclerosis (ALS). Specimens from six age-matched, neurologically normal control individuals were included for comparison. Examination of presynaptic terminals revealed a wide range of changes not only in degenerated neurons (central chromatolytic neurons), but, to a lesser extent, in normal-appearing neurons. The alterations included dense conglomerates of aggregated dark mitochondria and presynaptic vesicles, bundles of neurofilaments, as well as marked increase of presynaptic vesicles. Our observations suggest that in patients with ALS a substantial synaptic alteration does take place in the early stages of anterior horn neuron degeneration and degeneration of axosomatic synapses of anterior horn neurons in ALS may be of consequence on lower motor neuron degeneration.