In recent years an association between oral lichen planus (OLP) and HCV infection has been reported, but the frequency of this association seems to differ in the various geographic areas. It is clear, instead, that some abnormalities occur in the immune-regulation mechanisms of patients with OLP and it is thought to be due to the chronic antigenic stimulus of HCV that causes functional disorders of the immune system in infected patients. Possible immunologic difference between 17 patients with OLP and HCV+ and 17 patients with OLP and HCV- were investigated using standard immunofluorescence and flow cytometry techniques. The distribution of T and B cells was normal in all patients examined, while NK CD56+ cells were increased, above all in HCV- patients. About 65% of T CD4+ lymphocytes coexpressed the CD45RO isoform (p=0.002), while approximately 32% expressed CD45RA, without significant differences in comparison to HCV+ subjects (p>0.05). Moreover, almost all the CD4+CD45RO+ subpopulation coexpressed CD29 in all patients examined. No significant differences between the two groups of patients were detected as to the increase of cytotoxic T CD8+CD57+ lymphocytes. The B cells CD19+CD5+ responsible for the production of "natural" antibodies were detectable in both the examined groups, even if not in all HCV+ subjects (30% +/- 10.1 in HCV- and 27% +/- 19.4 in HCV+ patients; p=0.47). These findings suggest the existence of differences in lymphocyte subpopulations between OLP-HCV+ subjects and OLP-HCV- patients.