Serum and cerebrospinal fluid (CSF) of 56 patients with dementia of the Alzheimer type (DAT) and 33 healthy controls were examined in order to investigate intra-blood-brain-barrier (intra-BBB) synthesis of immunoglobulins. Intra-BBB immunoglobulin G (IgG) synthesis was defined as an elevated IgG index (greater than 0.7) and/or presence of oligoclonal IgG in CSF but not in serum on isoelectric focusing, and intra-BBB immunoglobulin M (IgM) synthesis as an elevated IgM index (greater than 0.06). In total, 10 (18%) DAT patients displayed an intra-BBB immunoglobulin synthesis--five (9%) an IgG and five (9%) an IgM synthesis--but none among the controls. Also, the DAT patient group showed higher mean IgG and IgM indexes than the control group. These findings support the hypothesis that immunological mechanisms may play a role in the etiology and/or pathogenesis of Alzheimer disease, at least in a subgroup of patients.