The current study analyses the ultramorphology, lymphocyte activation marker expression, DNA synthesis, and gamma-interferon and immunoglobulin production of inflammatory cells in oral lichen planus (OLP) lesions. According to these four different aspects of lymphocyte activation, only a minor fraction, 5% at the most, of all T cells in situ were activated. However, it is this minor fraction, and not the resting T cells without signs of activation, which may prove decisive for the outcome of the local immune-inflammatory process in OLP. We also studied both spontaneous and phytohaemagglutinin (PHA) stimulated peripheral blood T cell function. 3H-thymidine incorporation and gamma-interferon secretion were determined. Interleukin-2 (IL-2) receptor and major histocompatibility complex (MHC) locus II coded la antigen were stained with monoclonal antibodies. The peripheral blood T cell subsets and spontaneous MHC locus II antigen expression were similar in OLP patients and healthy controls, whereas spontaneous lymphocyte proliferation was lower in OLP patients (p less than 0.01). The PHA induced expression of IL-2 receptor and T cell proliferation were similar in both groups. Gamma-interferon secretion and MHC locus II antigen expression were low in OLP patients compared with the controls (p less than 0.01). The results suggest a defect in OLP T cell activation disclosed by in vitro PHA stimulation and occurring between IL-2 receptor ligand binding and gamma-interferon secretion. The findings of our peripheral blood mononuclear studies do not, however, provide an easy or straightforward explanation of the changes observed in the disease itself, particularly with respect to local pathogenesis.