Our prospective study consisted of a general and neurological evaluation in 48 patients (41 females, 7 males; mean age: 58.2 years) with primary Sjögren's syndrome (PSS). We performed serologic studies and cranial magnetic resonance imaging (MRI). Main extraglandular features were arthralgias and non-erosive arthritis (37.5%). Raynaud (21%) and pulmonary fibrosis (12.5%). Antinuclear antibodies were positive in 42.5% and anti-SS-A (Ro) in 20%. Migraine (52%), neuropsychiatric disease (29%) and a past history of focal acute neurological deficits (23%), were the central nervous system (CNS) manifestations more frequently observed. Cranial MRI examination detected hyperintense small subcortical lesions in 51.3% of patients and in 36.6% of age and sex matched controls (P < 0.001). CNS disease was not serious concerning vital prognosis, but produced significant morbidity in some patients. Late onset "migraine-like" episodes with prolonged sensoromotor deficits and coexisting neuropsychiatric disease emerged as a characteristic clinical spectrum in those patients diagnosed in a neurological setting. Cranial MRI was frequently abnormal, but findings were not specific. Neurologic manifestations reminiscent of multiple sclerosis were rarely seen.