This study investigated the use of anti-ribosomal P antibodies in the diagnosis of cerebral complications of systemic lupus erythematosus using two different methods-western blotting and enzyme-linked immunosorbent assay. Anti-ribosomal P antibodies in patient serum were detected in both methods using a purified ribosomal P antigen substrate. Western blotting detected anti-ribosomal P antibodies with a 90% specificity for systemic lupus erythematosus in 56% of patients with the disease. The detection of anti-ribosomal P antibodies by western blotting in patients with systemic lupus erythematosus was significantly associated with psychosis and/or seizures; detection was positive in 90% of patients with these cerebral complications and in 41% of those without. Elevation of the level of anti-ribosomal P antibody, as measured by enzyme-linked immunosorbent assay, was 99% specific for systemic lupus erythematosus in 44% of patients with systemic lupus erythematosus that was not associated with cerebral involvement. We conclude that the measurement of anti-ribosomal P antibodies by western blotting is helpful in the diagnosis of cerebral lupus in selected patients.