ABSTRACT: In peripheral neuropathies with monoclonal gammopathy, mainly IgM, it appears clear from clinical, electrophysiological, and experimental data, that the target glycolipid or glycolipid epitope for the IgM is related to the type of neuropathy-purely sensory, predominantly sensory, or uniquely motor. Investigations have focused on chronic peripheral neuropathies associated with polyclonal IgM reactivity to glycolipids. Although IgM anti-GM1 antibodies are present in normal controls, there is a subgroup of motor neuropathies with high titer anti-GM1 antibodies, mainly multifocal neuropathies with conduction blocks (MMNCB). Another subgroup of MMNCB may include IgM anti-SGPG antibodies that do not cross-react with MAG. The importance of the fine structure of the epitope has to be considered in view of the pathogenicity of the antibody. It may bear consequences on its binding properties on the neuronal surfaces and on its biological implications.