The aim of this research is to make a detailed analysis of neuromuscular transmission in human diseases affecting the neuromuscular junction. The proposed studies are concerned particularly with aspects of neuromuscular transmission in four newly recognized congenital myasthenic syndromes and in the myasthenic syndrome sometimes associated with oat cell bronchial carcinoma (Eaton-Lambert syndrome, ELS). Electrophysiologic methods will be used including electromyographic techniques to study the patient, and intracellular microelectrode techniques to record the events of neuromuscular transmission in single muscle fibers of biopsied muscles. The purpose is to determine in detail which step in the chain of events in neuromuscular transmission is abnormal and to identify causative factors. A search will be made for a circulating factor from the oat cell tumor as a cause of the defect of neuromuscular transmission in ELS. The possibility that the defect in ELS may result from an immune response to tumor antigens will be tested. Familial, congenital myasthenia gravis in dogs will be studied as a model for one form of congenital myasthenic syndrome in man. The long term goal is to improve criteria for the diagnosis of different defects of neuromuscular transmission in man and to provide information required for devising appropriate treatment.