Immunoglobulin (Ig) M concentration in cerebrospinal fluid (CSF) was measured in 30 reference subjects to determine reference ranges which were up to 0.41 mg/l for CSF IgM, 0.06 for IgM index, and 9 x 10(-4) mg/l for the Reiber empirical formula. Intrathecal IgM synthesis was then studied in 159 patients with different neurological diseases both by detecting CSF oligoclonal IgM bands and by determining the IgM index and Reiber's intrathecal IgM production values. At the same time, the state of blood-CSF barrier was evaluated in all patients by CSF polyacrylamide gel electrophoresis and by CSF/serum albumin ratio. Oligoclonal IgM bands were present mainly in patients with intrathecal humoral immune response, e.g. multiple sclerosis, other inflammatory nervous diseases, and infections of the central nervous system. Quantitative IgM ratios were, however, elevated in conditions not associated with local humoral immune response. Furthermore, quantitative ratios were elevated in patients with damaged blood-CSF barriers. Oligoclonal IgM bands are thus considered to be the most useful tool in detecting intrathecal synthesis of IgM.