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Arachnoiditis was produced experimentally in male albino ICR mice by intrathecal injection of meglumine iocarmate. A control group received intrathecal injection of an electrolyte solution resembling CSF. Eight weeks after injection, the brains and spinal cords were removed for brain beta-endorphin and spinal cord met-enkephalin measurement by radioimmunoassay, and the dural sacs were removed for histologic examination to confirm the presence or absence of arachnoiditis. Brain beta-endorphin content was significantly reduced and spinal-cord enkephalin concentration was significantly elevated in iocarmate-treated animals. The dura and arachnoid in the treated mice were thickened and infiltrated with lymphocytes. These studies indicate that arachnoiditis alters endogenous polypeptide concentrations.