The mechanism of motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is still unclear and the post-mortem analysis of samples from ALS patients does not permit a clarification of the early events of cell death occurring in ALS. Animal models of motor neuron degeneration represent a reliable tool to investigate the type of cell death. Attention was focused on the possible role of apoptosis in a spontaneous model of cervical spinal cord motor neuron degeneration, the wobbler mouse. Firstly, the rate of motor neuron loss occurring in the cervical spinal cord region of wobbler mice during different phases of symptoms progression was quantified by CholineAcetyltransferase (ChAT) immunohistochemistry. This was followed by a series of immunohistological studies to ascertain whether apoptosis was actually involved. ChAT immunostaining confirmed the severe loss of cholinergic neurons. Since the rate of motor neuron death is maximal in the first phase of the disease (from the 3rd to the 5th postnatal week), apoptotic markers were evaluated in 4-week-old wobbler mice. This study, carried out by examining a large number of cervical spinal cord sections from 20 affected animals and 20 healthy littermates, did not show either caspase activation or DNA fragmentation. These results strongly suggest that motor neuron death occurring in the wobbler mouse is not related to a caspase-dependent apoptotic mechanism.