A total of 11 cases of Waldenstróm's Macroglobulinemia (WM) have been investigated to study the association of the disease with neuropathy. A 53-year-old female patient (Wu) had a pronounced peripheral neuropathy, in which the role of IgM M-protein could be observed. Sections of Wu's biopsied sural nerve were subjected to light and electron microscopy and direct immunofluorescence (IF). Myelin degeneration with axonal change was found, while fluorescence reaction occurred in epineurium only. Sections of a healthy dog's sciatic nerve were submitted to purified IgM M-proteins from Wu and another WM patient (Kon) without neuropathy, respectively. Indirect IF showed a deposit of fluorescence on the myelin sheath by Wu's, but not by Kon's, M-proteins. It is proposed that an autoimmune mechanism underlies the peripheral neuropathy in the WM patient.