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Direct immunofluorescence (DIF) has been carried out in 66 sural nerve biopsies using antibodies against human IgG, IgA, IgM, C3, C4, albumin, fibrinogen, and ĸ- and λ-chains. In 37 out of 63 (59%) different neuropathies immunoglobulins or other plasma proteins were found within the peripheral nerves. IgM along the myelin sheaths were found in monoclonal IgM-K-associated demyelinating peripheral neuropathy and chronic inflammatory demyelinating peripheral neuropathy. IgM within the perineurium were detected in hereditary, diabetic, paraneoplastic, paraproteinemic and neuropathies of unknown cause. In inflammatory, vasculitic, hereditary and toxic neuropathies fibrinogen, albumin, IgG and IgA were variably observed in endoneurium, endoneurial vessels, perineurium and epineurial vessels. In our experience DIF appears to be just an unspecific marker of sural nerve pathology. In selected cases however DIF may be helpful in the diagnosis or in better understanding the pathogenetic mechanisms of the disease.