Lymphoid cells were isolated from human gingival tissues which were indexed clinically as normal, periodontal inflammation without pocket formation, and periodontitis or inflammation with pocket formation. These isolated gingival inflammatory cells were then assessed for their ability to kill gingival fibroblastsin vitroand to produce lymphotoxin withoutin vitrostimulation. Lymphocytes isolated from clinically normal gingival tissues showed no cytotoxic activity and did not produce significant amounts of lymphotoxin. Conversely, cells from inflamed tissues with no pocket were cytotoxic at a low level for gingival fibroblasts and produced some lymphotoxin. Cells isolated from periodontitis tissues (inflamed with pocket) showed a greater degree of cytotoxicity for the fibroblasts. and the activity increased with increasing numbers of lymphoid cells. These cells appeared to be very active. since a ratio of one lymphocyte per fibroblast still showed significant killing. In addition, lymphotoxin was elaborated by these periodontitis lymphocytes in culture. These data indicated that a local hyperimmune response was present in chronically inflammed gingiva and that the lymphoid cells were activated and had the potential for tissue destruction.