The state of the immune system, both humoral and cell-mediated, was evaluated in motor neurone disease (MND) patients. The data obtained for the MND patients were confronted with normal controls and a group of patients affected by nervous diseases not involving the immune system. Some differences were observed between MND patients and normal subjects, namely: increase of WBC and γ-globulin in MND patients. However, such differences were not observed between MND patients and pathological controls, and therefore are probably due to a higher frequency of infectious complications in MND patients in respect to normal controls. The capacity of the immune system to respond to an adequate stimulus was normal, and no precipitating anti-CNS antibodies were detected in MND sera. Furthermore, no sex-linked differences were observed and the CSF abnormalities observed in 2 out of 16 MND patients were probably reflecting only destruction of CNS cells. The data are discussed in view of the possible pathogenetic mechanisms of MND.