Objectives - To characterise phenotypically the minor salivary glands of patients with clinical and histological features of Sjogren's syndrome (SS) infected with hepatitis C virus (HCV). Patients and Methods - 75 consecutive patients with SS (31 primary SS, 44 secondary SS) diagnosed by preliminary European classification criteria. The presence of anti-HCV antibodies was detected by commercial third generation ELISA and by a second generation immunoblot assay. Presence of HCV genome in serum was determined by polymerase chain reaction analysis. Expression of CD3, CD4, CD8, CD20, HLA- DR, and CD25 molecules in lymphocytic and epithelial cells on minor salivary glands was detected by immunohistochemical assays. Expression of interferon y and interleukin 4 cytokines was determined by in situ hybridisation. Results - Six of 31 primary SS (19%) and one of 44 secondary SS (2%) serum samples were positive for anti-HCV by ELISA. Three samples were positive, three indeterminate, and one sample corresponding to a secondary SS patient was negative by immunoblot. The three immunoblot positive serum samples were also HCV-RNA positive by PCR assay. The study of lymphocytic cells in the diffuse infiltrate of minor salivary glands showed a predominance of the CD3 lymphoeytic population. A predominance of CD4 over CD8 T cells (ratio 2:1) was observed in HCV and non- HCV infected patients. The analysis of the lymphocytic focus showed that the HCV infected patients had a predominance of CD20 positive cells. Activation molecules (CD-25 and HLA-DR) were expressed in HCV and non-HCV infected patients in lymphocytic and epithelial cells, however epithelial cell expression of CD25 was low in HCV infected patients. As expected, a pronounced Th1 response was observed in the lymphocytic foci of HCV patients. Conclusions - HCV infected patients may develop an autoimmune sialadenitis, similar to that described in primary SS.