Thirty-seven serum and 37 cerebrospinal fluid (CSF) specimens from 27 patients with subacute sclerosing panencephalitis (SSPE) were tested for measles virus (MV) IgM antibodies and IgM-class rheumatoid factor (RF) to determine if a temporal relationship exists between SSPE onset and these immunoglobulins. Sensitive solid-phase radioimmunoassays were used for immunoglobulin detection. Five of six MV IgM-positive CSF, both MV IgM-positive sera and six out of eight sera with elevated RF levels were collected within 1 yr of SSPE onset. Also collected during this time were six other sera having high binding in the MV IgM assay, which was not due to MV-specific IgM antibodies. Two of these sera had as high or higher binding of IgM to a Vero cell control antigen, suggesting involvement of an IgM-class autoantibody. The other four sera had false-positive MV IgM assay results due to RF interference. RF interference was dependent on both the titer and avidity of the MV IgG antibodies involved. Three conclusions can be drawn from these results. First, MV IgM antibodies and elevated RF levels are not markers for acute SSPE, despite the tendency for their synthesis at this stage of the disease. Second, immunoassay analysis of viral IgM antibodies must employ an appropriate control antigen to account for background IgM binding. Finally, even if RF levels are normal or near normal, a false-positive IgM immunoassay result can still occur if antigen-specific IgG antibodies in the same sample have the right combination of titer and avidity.