The sera of 9 patients with benign IgM paraproteinaemia and chronic sensorimotor neuropathy were tested for reactivity to human peripheral nerves by the indirect immunoperoxidase method. They reacted in very high titre (10(-3)-10(-6) with a cytoplasmic Schwann cell component, and to lesser degree, with peripheral nerve myelin (10(0)-10(-3). The Schwann cell staining was in the form of perinuclear cytoplasmic granules and was only seen with adult nerve. The distribution of the antigen was similar to that of the metachromatically staining Pi-granules of Reich, which accumulate in the peripheral nerves with age. Specific activity was present in the IgM and F(ab)2 fractions and could be absorbed out with peripheral nerve tissue, but not with liver. Reactivity is not a simple function of the IgM level, since many IgM paraproteins do not react. The antibody is species specific and binds to human, but not to any component of rabbit, rat or guinea pig sciatic nerves. Antigenicity is removed by pretreatment of the nerve with chloroform-methanol or periodate, but not protease or trypsin. Reactivity is restored, after periodate treatment, by exposure to sodium borohydride. It is suggested that some IgM paraproteins have a specificity for a myelin glycolipid or glycoprotein, which normally accumulates in the Pi-granules of the Schwann cell cytoplasm as a function of age.