Cerebrospinal fluid (CSF) and sera from 17 patients with primary Sjögren's syndrome (PSS) with or without clinical evidence of nervous system involvement were studied. Intrathecal IgG synthesis as measured by oligoclonal IgG bands on agarose isoelectric focusing or elevated IgG index in CSF was found in 6 of 8 patients with clinical nervous system involvement but also in 5 of 9 patients without clinical nervous system involvement. Elevated IgM-index in CSF was found in 7 of 8 patients with clinical nervous system involvement and in 6 of 9 patients without clinical nervous system involvement. By immunoblotting, CSF IgG-antibodies against myelin basic protein (MBP) were found in 3 of 12 patients with multiple sclerosis (MS), but in none of the patients with PSS or in the 12 controls. Intrathecal anti-viral IgG-antibodies, as measured by immunoblotting against measles, mumps, varicella or herpes simplex, were found in 8 of 17 patients with PSS, and in 7 of 12 patients with MS, but were not detected in the controls. Our observations support the concept that the central nervous system (CNS) is included in the multiple immunological phenomena of PSS. Interestingly, in some PSS patients intrathecal IgG synthesis occurred without overt clinical nervous system involvement and thus the clinical significance of intrathecal IgG synthesis in PSS is uncertain. The similarities with MS regarding intrathecal antiviral antibody production may be interpreted as the result of polyclonal B-cell activation.