Immunoregulatory control at both a local and systemic level is likely to be an important factor in the control of chronic inflammatory periodontal disease, explaining, at least in part, the individual variations between patients as well as the cyclical nature of the disease process. The autologous mixed lymphocyte reaction (AMLR), which is due to the stimulation of T cells by autologous HLA-DR positive non-T cells in the absence of specific antigen, is thought to be an in vitro correlate of immunoregulation. It is possible therefore, that the AMLR may detect systemic immunoregulatory phenomena in chronic inflammatory periodontal disease and that aberrations in the AMLR may be a manifestation of the disease and in turn reflect disease activity. Recent evidence does in fact suggest that the peripheral blood AMLR may identify particular disease groups, provided age and time of peak responsiveness are taken into account and hence may have an epidemiological application. It remains to be determined, however, that when used in a longitudinal fashion, the AMLR does reflect individual disease activity. These results are reviewed and areas of future research discussed.