Quantitative analysis of peripheral blood lymphocytes was carried out in 25 patients with atrophic-erosive type of oral lichen planus (OLP) (Group 1), in 28 patients with reticular-plaque like lesions of OLP (Group 2) and in 21 healthy patients (Group 3) by using flow cytometry. CD4+ subsets decreased significantly in patients with reticular-plaque like varieties when compared with healthy patients (Group 3) (One way analysis of variance p = 0.039; t-test with Bonferroni correction p < 0.05). Moreover, in patients with hyperkeratosic forms of OLP (Group 2) CD8+ cell populations were significantly higher than in controls (Group 3) (Kruskal-Wallis test p = 0.035; Mann-Whitney test with Bonferroni's correction p < 0.0001) and consequently CD4/CD8 ratio was significantly lower in patients with reticular-plaque like lesions than in controls (Kruskal-Wallis test p = 0.01; Mann-Whitney test with Bonferroni's correction p = 0.013). No statistical differences between patients of Group 1 (atrophic-erosive OLP) and the other two Groups (hyperkeratosic OLP and healthy controls) were detected. 40% of the patients of Group 1 were affected by chronic hepatopathies, most of which were related to hepatitis C virus (HCV), but the data were not substantially modified after adjustment for the patients with chronic liver disease HCV positive. There is no clear evidence that these results indicate the existence of a different pathogenetic mechanism between erosive-atrophic and hyperkeratosic types of OLP. On the other hand, these results and the previously reported immunohistochemical findings suggest that quantitative alterations of peripheral blood lymphocytes in hyperkeratosic varieties of OLP could represent a shift of CD4+ cells from the vascular to the oral mucosa compartment.