Sjögren's syndrome (dryness of eyes, mouth, and other mucous membranes) may be associated with disease of joints, blood, internal organs, skin, and central and peripheral nervous systems. We reviewed 33 cases of primary Sjögren's syndrome and peripheral neuropathy evaluated by neurologic examinations and EMG at the Mayo Clinic from 1976 to 1988, and studied sural nerve biopsy specimens in 11 of them. Symmetric sensorimotor polyneuropathy occurred most frequently, followed by symmetric sensory neuropathy. Autonomic neuropathy, mononeuropathy, or cranial neuropathy (especially trigeminal neuropathy) was superimposed on generalized neuropathy in approximately one-fourth of patients. The course generally was slowly progressive, except for a few patients who may have improved with prednisone therapy. Although spinal ganglion involvement might have accounted for some of the clinical and neurophysiologic findings, we found evidence that necrotizing vasculitis was involved in fiber degeneration. All nerve biopsies revealed perivascular inflammatory infiltrates and other vessel abnormalities, which were diagnostic in two cases and strongly suggestive of necrotizing vasculitis in six cases. Axonal degeneration predominated over demyelination and sometimes was focal or multifocal. In neuropathy of unknown cause, particularly if it is sensory, autonomic, or involves trigeminal nerve, consider Sjögren's syndrome.