Autoantibodies that interfere with neurotransmitter release by affecting the function of voltage-operated calcium channels (VOCCs) have been found in patients with Lambert-Eaton myasthenic syndrome (LES). To find out the nature of the antigen to which these autoantibodies bind, tests were done with omega-conotoxin, which blocks some types of VOCCs. LES antibodies were able to immunoprecipitate VOCCs prepared from the human neuronal cell line IMR32 which were pre-labelled with the specific VOCC ligand omega-conotoxin. LES autoantibodies are also able to specifically down-regulate the expression of VOCCs in IMR32 cells. A new radioimmunoassay for the quantitative detection of LES antibodies was developed and found to be of value in distinguishing LES patients from patients with myasthenia gravis and some other neurological disorders.