Psychiatric manifestations are relatively common in systemic lupus erythematosus (SLE) patients. Since there are factors causing psychiatric manifestations other than SLE, the diagnosis of lupus psychosis (LP) is often difficult. Previous studies disclosed that cerebrospinal fluid (CSF) IL-6 was elevated in SLE patients with neuropsychiatric manifestation. The current studies were therefore designed to examine the efficacy of CSF IL-6 in diagnosis of LP. Multicenter retrospective study was performed with 45 SLE patients who showed psychiatric manifestations between 1993 and 2000. The diagnosis of LP and psychosis due to causes other than SLE (non-LP) was confirmed by retrospective review of the clinical records. Thirty-two of the 45 patients were reconfirmed as LP in the retrospective study. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of CSF IL-6 for diagnosis of LP were 87.5% and 92.3%, respectively, at the cut-off value of 4.3 pg/ml. These results indicate that CSF IL-6 might be an effective measure in diagnosing LP, although exclusion of infectious meningoencephalitis and cerebrovascular accident is necessary.