The etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are still unknown. Autoimmune mechanisms are considering to be possible causes of ALS, among several other possible mechanisms. In this paper, we describe the determination of autoantibodies against proteins of the brain motor zone and skeletal muscular system in the sera of patients suffering from ALS. Autoantibodies against carbonyl reductase 1, α-enolase, 2′,3′-phosphodiesterase of cyclic nucleotides, and pyruvate kinase 3 (isoform 2) were primarily found in the motor zone, whereas those against muscular creatine phosphokinase, myoglobine, carboanhydrase III, and troponin 1 of the fast type were identified in the skeletal muscle in the majority of patients with ALS. In addition, dynamic changes in the structure of the troponin complex were demonstrated in the tissue of skeletal muscle. The significance of the presence of autoantibodies against proteins of the brain motor zone in the sera of ALS patients is unknown. These autoantibodies most likely appeared as a secondary immunological effect of neuron damage. We can also conjecture that they accelerate the affection of muscle tissue and motoneurons. © Pleiades Publishing, Ltd. 2007.