The macrophage migration inhibition factor assay was used as a specific measure of cellular hypersensitivity to peripheral nervous system antigen in a large group of Guillain-Barré patients and control subjects. Lymphocytes from 34 patients with Guillain-Barré syndrome, 33 with other peripheral nervous system disease, and 33 normal controls were assayed for production of macrophage migration inhibition factor. A mean of 101 ± 7.2 was obtained in the control group, 70 ± 16.3 in the Guillain-Barré syndrome group, and 96 ± 11.3 in those with other peripheral nervous system disease. Twenty-six of the 34 patients with Guillain-Barré syndrome, two patients with myeloradiculitis, and two with Bell's palsy gave significant values. These results support the hypothesis that cellular hypersensitization to peripheral nervous system antigens is a pathogenetic factor in Guillain-Barré syndrome.