Clonally restricted anti-IgG antibodies were detected, by isoelectric focusing (IEF) and chromatofocusing techniques, in the sera of patients with rheumatoid arthritis (RA). Anti-Fab antibodies were predominantly acidic proteins with isoelectric points of 4.5-6.5 and displayed restricted spectrotype patterns. Proteins reactive with the Fc portion of IgG showed polyclonal spectrotype patterns with alkaline PI of 7.5-9.0. A limited array of anti-Fab spectrotypes was consistently detected in RA sera when analyzed by IEF on 6M urea gels. Additional anti-Fab antibody bands were detected when the RA sera were dialyzed against 4-6M urea prior to IEF analysis, indicating that some anti-Fab antibodies exist in a complexed form in serum. Under these dissociating conditions, anti-Fab antibodies could also be detected in normal subjects, but the spectrotype patterns were more restricted than those in RA sera. Because anti-Fab antibodies may regulate normal immune responses, the increased quantity of clonally restricted ,anti-Fab antibodies in RA may indicate an abnormality of this immunoregulation.~~p -