SUMMARYTh2 cells are more abundant than Th1 cells in periodontitis lesions, but the relative importance of the Th1 and Th2 subsets in periodontal disease is not understood. In addition, the role of proinflammatory and anti-inflammatory cytokines in this disease process is unclear. Biopsies were obtained from 10 patients with early onset periodontitis (EOP) and 10 patients with adult periodontitis (AP). From all of the patients in the AP group we were able to obtain and section the gingival tissue to serve as controls. We used polyclonal monospecific antibodies to detect cells expressing IL-2, IL-4, IL-6, IL-10 and IL-15, tumour necrosis factor (TNF-a ) and interferon-gamma (IFN-g) in formalin-fixed, paraffin-embedded sections of granulation tissue from periodontitis lesions. We also employed a series of oligonucleotide probes to detect cells expressing the cytokine transcripts in the same tissue biopsies. Cells that expressed IL-4 or IL-6 were more numerous than cells expressing either IL-2 or IFN-g. Th2 cells were more numerous in EOP and AP tissues. IL-15 substitutes for IL-2 in a number of biological activities related to the Th1 immune response, and interestingly, in periodontal lesions the IL-15-expressing cells outnumbered IL-2-expressing cells, suggesting that this is the pattern of immune regulation by T cells in the periodontium. The functional balance in the T cell subsets detected by their cytokine profiles underlies the importance of the anti-inflammatory mechanisms taking place in the diseased tissue. The numbers of inflammatory leucocytes that express the anti-inflammatory cytokine IL-10 are much more widely distributed than those that express the proinflammatory cytokines IL-6 and TNF-a . This study suggests that large numbers of infiltrating inflammatory cells as well as accessory cells are involved in the down-regulation of the inflammatory and immune response in periodontitis.