Solubilized dental plaque is mitogenic for nylon woolpurified human cord blood T lymphocytes. Journal of Periodontal Research 1987; 22:94-102. Human cord blood T lymphocytes were purified by filtration through nylon wool columns and tested for their ability to synthesize DNA in response to stimulation with solubilized dental plaque, phytohemagglutinin and streptolysin O. Ninety out of 106 cord blood T lymphocyte preparations (85%) responded significantly (p<0.05) to solubilized dental plaque. DNA synthesis was maximal after 7 days of culture; 20 fig of solubilized dental plaque was the optimal dose. A similar frequency of significant responses (89%) was obtained with the T lymphocyte mitogen, phytohemagglutinin; however, streptolysin O, an antigen, stimulated only 23% of the T lympyhocyte preparations significantly. The high frequency of significant cord blood T lymphocyte responses to solubilized dental plaque was not affected by maternal periodontal status, nor could any evidence be found for the removal of adherent suppressor cells by the nylon wool purification. Furthermore, cord blood leukocyte and mononuclear cell cultures responded about as frequently as, and synthesized more total DNA than T lymphocyte cultures to solubilized dental plaque. Freshly prepared solubilized dental plaque was shown to contain inhibitors as well as activators of lymphocyte transformation, and was significantly less immunogenic (mitogenic) than an older, frozen preparation of solubilized dental plaque. These results indicate that solubilized dental plaque contains one or more mitogens for human T lymphocytes.