Objective. To determine the serum autoantibody profile in an adult patient with systemic lupus erythematosus manifested by complete heart block (CHB) and seizures, and to investigate the source of autoantibodies found in the patient's cerebrospinal fluid (CSF). Methods. The serum and CSF autoantibody profiles were determined by serologic testing and Western blot studies. An antibody activity index was devised to determine the source of the autoantibodies found in the CSF. Results. The patient's serum contained anti‐SS‐A (52 kd and 60 kd), anti‐SS‐B, anti‐U1 RNP, and anti‐Sm autoantibodies. Studies of her CSF, however, revealed only anti‐SS‐A and anti‐SS‐B autoantibodies, with a high antibody activity index. Conclusion. The finding of anti‐SS‐A (52 kd and 60 kd) and anti‐SS‐B autoantibodies was similar to reported findings in congenital CHB. Intrathecal synthesis of anti‐SS‐A and anti‐SS‐B was the source of autoantibodies found in the CSF. This patient's symptoms may be pathophysiologically linked to an immune reaction between the anti‐SS‐A and anti‐SS‐B autoantibodies and neural tissue in the brain and heart.