A qualitative and quantitative immunohistological investigation was performed on biopsies of oral ulcers from patients with Behcet's syndrome (BS) and those with recurrent oral ulcers (ROU). The results were compared with control oral biopsies from patients with other diseases and normal oral mucosa. The expression of HLA-DR on the cell membrane of keratinocytes was found in 13 out of 15 lesions from patients with BS and ROU, as compared with only one out of 15 controls. The relative density of HLA-DR was investigated quantitatively by microdensitometry and this confirmed that DR expression in the epithelial cells of patients with BS and ROU was significantly greater than in diseased and normal control oral tissues. A prominent mononuclear cell infiltration consisted predominantly of T lymphocytes and mature macrophages. Analysis of the CD4 and CD8 subsets of T cells failed to show significant differences between BS, ROU and control diseased tissues. Increased numbers of Langerhans cells were found in the epithelium by morphometric analysis with the CD1 monoclonal antibody in BS and ROU but an increased number was also found in lichen planus. The results suggest that the immunohistological changes in oral lesions of BS and ROU manifest an enhanced immune response in the epithelium, keratinocytes express HLA-class II antigen and increased number of Langerhans cells as well as in the lamina propria with a prominent infiltration of CD4, CD8 and macrophage-like cells. The characteristic pattern of exacerbations and remissions of oral ulceration can be interpreted by the hypothesis that an initiating microbial agent may induce a mononuclear cell infiltration, with the release of cytokines, expression of class II antigen in keratinocytes and causing ulceration, followed by down-regulation of immunity by tolerant T cells induced by the class II positive keratinocytes, leading to a remission.