Our purpose was to evaluate the role of Epstein-Barr virus (EBV) in the production of antiperinuclear factor (APF), a rheumatoid arthritis (RA)-specific marker, and the autoimmunogenicity of 'perinuclear antigens' (PNA) found within the buccal mucosa epithelial cells used as a substrate in the APF assay. Fifty APF-positive and 50 APF-negative sera from RA patients were examined for the presence of antibodies to six different EBV antigens. APF was tested in the serum of 40 patients with acute infectious mononucleosis (IM), 48 PNA-expressing donors and 29 non-PNA-expressing donors. The EBV genome was sought in the saliva and buccal cells of both types of donors. The targeted granules of cells from a PNA-expressing donor were studied by electron-microscopy. The prevalence of anti-EBV antibodies was similar in RA patients with and without APF, whereas the APF-positive sera was elevated in acute IM. The titres of anti-EBV antibodies did not correlate to the expression of PNA in the buccal cells of the donors. There was no relationship between this expression and the presence of the EBV genome in the material obtained from 'positive' donors, relative to 'negative' donors. No virus-like particles could be detected inside the granules by electron microscopy. These results indicate that there are no direct relationships between EBV and the APF/PNA system, although APF was present in a number of patients with IM.