We have proposed a novel overall hypothesis and approach to understanding the pathophysiology of adult periodontitis, one of the most common diseases that afflicts the US population. While mortality of the dentition is the most familiar outcome of adult periodontitis, its links with other more severe diseases, including coronary artery disease, respiratory diseases and pre-term labor, cannot be ignored. We have called attention to the many intriguing parallels between adult periodontitis and contact hypersensitivity (CHS). CHS is among the most common of dermatoses that afflicts mankind and one of the most intensively studied of in vivo immune responses. Both adult periodontitis and CHS target the host integument (gingiva or skin) and appear to involve the activation and sensitization of similar subsets of antigen capture and presenting cells, the dendritic cells (DCs), as well as similar T cell subsets. DCs have been termed "nature's adjuvant", being more efficient at antigen-presentation than macrophages or B cells and the only antigen-presenting cells that can stimulate naïve T cells to proliferate. This immunostimulatory capacity can also have detrimental effects for the host, as typified by graft-vs.-host disease and CHS responses. Both AP and CHS involve a predominantly destructive T cell response mediated by both regulatory and effector T cells. In the present paper, we show intriguing evidence that Porphyromonas gingivalis is a unique pathogen in this regard, able to infect, sensitize and activate DCs in vitro and, probably, in situ. Many questions about the role of P. gingivalis-sensitized DCs in adult periodontitis, and of the parallels between adult periodontitis and CHS, however, remain to be answered.