Anti-sulfatide antibodies are associated with polyneuropathies having a prominent sensory component, but with variable degrees of motor and sensory loss, gait dysfunction and demyelination. In this study, we asked whether patterns of IgM binding to neural tissue in anti-sulfatide serums also demonstrated heterogeneity. We used immunocytochemical methods to examine IgM binding to peripheral nerve, dorsal root ganglion, and cerebellum in 41 serums with high titers of IgM anti-sulfatide antibodies. Our results showed that there were several different patterns of IgM binding to neural tissues in anti-sulfatide serums. In peripheral nerve the most common targets of IgM were axons, resident macrophages or Schwann cell cytoplasm. In the cerebellum, IgM bound to neuronal nuclei, white matter, or neuropil in molecular and granule cell layers. There was little binding of IgM to structures in the dorsal root ganglion. Patterns of IgM binding to peripheral nerve and cerebellum were related. Binding to neuronal nuclei in the cerebellum was usually found in serums that recognized peripheral nerve axons or macrophages. Serums with binding of IgM to cerebellar white matter usually recognized Schwann cell cytoplasm. We conclude that IgM anti-sulfatide antibodies may have several different tissue binding patterns in the peripheral and central nervous systems. These differences may be related to the variation in clinical neuropathy syndromes associated with apparently similar anti-sulfatide antibodies.