Neuropsychiatric symptoms are often seen in patients with systemic lupus erythematosus (SLE). To investigate the relationship between involvement of the nervous system and clinical factors, including autoantibodies and the activity of SLE, we retrospectively reviewed 25 patients with neuropsychiatric SLE (NPSLE, mean age: 35.2+/-12.2 years). As controls 37 SLE patients without neuropsychiatric manifestations (mean age: 31.8+/-15.8 years) were employed in this study. At the onset no significant differences were seen in any clinical factors between the patients and the controls except for serum antinuclear antibodies. In relapse, the patients with NPSLE showed significantly lower levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores without neuropsychiatric evaluation (p<0.0001), erythrocyte sedimentation rate (ESR, p<0.005), and antinuclear and anti-double-stranded DNA antibodies (p<0.005) and higher WBC values (p<0.05) than at the onset. Also in the patients with relapsing NPSLE similar significant differences were seen in these parameters between onset and relapse (p<0.005). Despite a lack of significant differences, the cerebrospinal fluid showed lower values in cell counts, total protein, and IgG in relapse than at onset. These results suggest that there are no clinical factors that predict the development of NPSLE and that relapse can occur with low disease activity in the nervous system even with an inactive state of other organ involvement. Since NPSLE may suddenly relapse with a slight change in common disease activation markers, including inflammatory reactions, autoantibodies, and complements in serum and CSF findings, adequate corticosteroid and/or immunosuppressive agents should be given at the onset and gradually be tapered after recovery, while looking out for recurrence.