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Human sera from patients with IgM paraproteinaemia were screened for IgM binding to frozen sections of the rat cerebellum by the indirect immunoperoxidase procedure. Out of 18 patients with a benign IgM gammopathy and associated demyelinating polyneuropathy (PPN), 17 showed binding to the surface of specific neurons, i.e. those of the deep cerebellar nuclei and the intermediate cell of Lugaro. Examination of other regions of the mouse brain suggests that the reactivity is restricted to cells of certain nuclei of the sensory-motor system. The use of F(ab)2 and monoclonal anti-idiotype antibodies demonstrate that the binding involves the antigen binding sites of the paraprotein. This reactivity indicates that some neurons have on their surface an antigen having an hapten in common with human myelin-associated glycoprotein (MAG) and the pi granules of human Schwann cells and furthermore is an additional serological characteristic of this group of patients. In addition 3 sera from the PPN group stained a particulate component in the cytoplasm of all medium-sized and large neurons. A similar staining was found with 7 out of 52 other unselected IgM paraproteinaemias.