It is important to remember that the merits of the different approaches to epitope mapping should be judged against the purpose of the study. A peptide specifically recognized by nearly all sera containing a certain autoimmune specificity [20, 21, 26], would most likely be selected for the detection of the anti-linear/continuous epitope fraction among those autoantibodies and could be highly useful for diagnostic purposes. This is true even if a majority of the antibodies were directed against conformational/discontinuous protein epitopes. If the purpose is to study the induction or maintenance of the autoimmune response, one would also have to look at and account for the conformation-dependent autoantibodies. There is also the possibility that some pathogenic autoantibodies could constitute a small fraction requiring the complete nucleic acid-protein complex as an antigen. In that case, the ‘pathogenic’ epitope would not be identified nor mapped using the techniques discussed in this review.