In order to study the relationships between the circulating IgG autoantibodies to epidermal cytokeratins (AECK), which were described in normal human sera as well as in sera from patients with various diseases, and the so-called 'antikeratin' IgG antibodies ('AKA'), which are highly specific for rheumatoid arthritis (RA), we simultaneously investigated AECK by a specific ELISA using cytokeratins from human stratum corneum (SC) and 'AKA' by semiquantitative indirect immunofluorescence assay on rat oesophagus epithelium, in a large series of 595 rheumatic sera including 229 RA. AECK were found to be present in all the 595 sera, with large inter-individual variations in titre. Whatever the titre chosen as threshold, the autoantibodies (auto-Ab) were never found to be specific for any rheumatic disease. Moreover, in RA, they were found to vary independently of IgM rheumatoid factor (IgM-RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), while they were found to vary in parallel with the total serum IgG concentration. In contrast, although 568 of the 595 rheumatic sera contained antibodies that labelled the rat oesophagus SC, the highest titre-like values were obtained with RA sera. At a convenient threshold, 95 (41.5%) of the 229 RA were detected while only three false positives (0.08%) remained among the 366 non-RA sera. Moreover, in RA, 'AKA' were found to be related to IgM-RF, ESR and CRP, while their titre was found to be independent of the total serum IgG concentration. Lastly, no statistical correlation was found between the antibodies, either in the whole sample of 595 sera or in any diagnostic group. In conclusion, the simultaneous investigation of AECK and 'AKA' showed that they differ from each other in all the aspects explored. AECK belong to the widely explored family of natural auto-Ab against cytoskeleton components and do not constitute a diagnostic marker while, on the other hand, 'AKA' confirmed their high diagnostic specificity for RA. It can also be asserted that, in spite of their name, 'AKA' do not recognize human epidermal cytokeratins, at least in the denatured form they present in ELISA. Therefore, they recognize either conformational epitope(s) appearing on cytokeratins during the late stages of the cornification process, or epitope(s) borne by rat cytokeratins but absent on human cytokeratins, or lastly a non-cytokeratin SC antigen.