Motor evoked potentials (MEPs) to magnetic trans cranial stimulation (TCS) were recorded in 47 patients with amyotrophic lateral sclerosis (ALS) in order to evaluate both excitability and conductivity changes relating to central motor pathways. The results were compared with those obtained from a control population of 43 subjects, 34 patients with definite multiple sclerosis (MS) and 15 patients with a rigid early from of Parkinson's disease (PD). The excitability threshold to TCS was higher in ALS patients for both upper and lower limbs compared with both controls and PD patients, but lower than that of MS patients. The Silent Period duration (SP (hand recordings): 80.1 ms, SD: 38.5) was significantly shorter in ALS patients than in all the other examined subjects (P < 0.001), nor did it increase proportionally to TCS intensity as with control subjects. The abnormal behavior of the SP appears to be specifically linked to the ALS disease, since it was neither observed in PD patients, nor in those with multiple sclerosis, who, on the contrary, displayed a prolonged mean duration of the SP (161.6 ms, SD 77 vs. 115.7 ms, SD 62 for the control group). Due to the neuronal loss of the largest neurons in ALS, MEP latency, amplitude, duration and the motor central conduction time (CCT) were in different proportion found abnormal. Our study shows how different neurological diseases with central motor involvement share broadly similar MEP abnormalities, but a different involvement of the silent period. We suggest that in ALS patients there may be abnormalities of motor cortical inhibitory mechanisms which are detected with the measurement of the SP. The distinctive 'depression' of this parameter in the case of ALS could be a significant marker for diagnosing this disease.