A sensitive and specific enzyme linked immunosorbent assay (ELISA) utilizing human recombinant acetylcholinesterase has been employed for the detection of human antibodies to human acetylcholinesterase. The method can detect allogenic antibodies to the Yt(a) form of human erythrocyte AChE. Adaptation of this ELISA method allowed the IgG subclass typing of IgG anti-AChE antibodies, which could help to determine the possible role of these antibodies in the aetiology of any neurological conditions. Routine serological investigations established the AChE phenotype of each of the patients recruited, to determine whether anti-AChE antibodies were allogenic or autogenic in origin. These techniques were used to determine the incidence of autoantibodies to AChE in patients with neurological conditions, including the subtypes of motor neuron disease. The data presented are not consistent with earlier reports of a high incidence of autoantibodies to AChE in amyotrophic lateral sclerosis and progressive muscular atrophy.