This study was undertaken in an effort to understand the role of cytokines on human gingival fibroblasts and T lymphocyte trafficking into inflamed gingival tissue. Using flow cytometry we examined gingival fibroblasts to determine the level of cell surface expression and the percentage of cells positive for intercellular adhesion molecule 1 (ICAM-1), the HLA-DR antigen, lymphocyte function-associated antigen 3 (LFA-3), and the CD44 molecule, which are involved in antigen presentation. The following cytokines were used: interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-6, and IL-8. The levels of ICAM-1 expression were enhanced in a dose- and time-dependent manner by IL-1 beta, TNF-alpha, or IFN-gamma, but not by IL-6 or IL-8. HLA-DR surface expression was induced only by IFN-gamma in a dose- and time-dependent manner, but not by the other cytokines tested. In contrast, the expression of LFA-3 and the CD44 molecule could be detected without the stimulation of any cytokine, but the levels of their expression were not significantly changed by any cytokines. The enhanced ICAM-1 expression by cytokines was reduced in a time-dependent manner following the removal of cytokines from the reaction mixture, while IFN-gamma-induced HLA-DR expression was maintained even 7 days after the removal of IFN-gamma. These data support an interactive role for inflammatory cytokines and the expression of adhesion molecules on gingival fibroblasts in the pathogenesis of gingival inflammation in periodontal disease.