Noncarcinomatous Lambert-Eaton myasthenic syndrome (LEMS) often associates with autoimmune disorders. A course of plasma exchange in both carcinomatous and noncarcinomatous LEMS induced clinical and significant electromyographic improvement which reached its peak 10 to 20 days after the last exchange. Prednisolone and azathioprine treatment was associated with striking clinical and electromyographic improvement in the 3 noncarcinomatous patients. The IgG fraction of LEMS plasma, and to a lesser extent plasma itself, injected daily intraperitoneally into mice induced similar electrophysiological changes to human LEMS, the reduction in the quantal content of the end-plate potential (epp) in diaphragm being highly significant. A train of stimuli at 40 Hz produced early facilitation or a less marked decline in epp amplitudes than occurred in mice injected with control IgG. The results indicate that the electrophysiological abnormalities in both forms of LEMS arise from an IgG autoantibody that binds to nerve terminal determinants which are concerned with the quantal release of transmitter.