Purpose: To understand the contribution of stromal cells, such as granulation tissue fibroblasts, to peri-implantitis with regard to (1) the secretion of constitutive factors promoting migration/survival of infiltrates into osseointegrated sites; and (2) the effect of exogenous infiltrate cytokines on the cells' secretion. Materials and Methods: Fibroblasts were cultured from eight peri-implantitis sites. Multiplexed enzyme-linked immunosorbent assay was used to quantify factors secreted by the cells either unstimulated or stimulated with gamma interferon (IFNg), interleukin 4 (IL4), or tumor necrosis factor alpha (TNFa). Controls consisted of fibroblasts cultured from healthy gingival and chronic periodontitis granulation tissues. Results: Peri-implantitis fibroblasts differed significantly from periodontitis fibro-blasts in their reduced secretion of the collagen inducer transforming growth factor beta-1 (TGFb1) and tissue inhibitor of metalloproteinase-1. The cells exhibited enhanced secretion of angiogenic factor vascular endothelial growth factor (VEGF) and collagenolytic matrix metalloproteinase 1 (MMP1) compared to both healthy and periodontitis fibroblasts. Fibroblasts from both periodontitis and peri-implantitis sites exhibited a pronounced proinflammatory profile compared to normal gingival fibro-blasts with respect to secretion of chemokines IL6, IL8, and monocyte chemoattractant protein 1 (MCP1). Fibroblasts stimulated with TNFa showed increased levels of IL6, IL8, MCP1; neutrophil chemokine growth-related oncogene alpha stimulation with IFNg increased MCP1; and stimulation with IL4 increased VEGF. Conclusion: The results indicate that peri-implantitis fibroblasts represent a distinct stromal population. The cells might participate in the pathogenesis of peri-implantitis by up-regulating both vascularity and matrix breakdown, thus promoting migration/maintenance of infiltrates into the site. Cytokines produced by infiltrates could enhance the inflammatory nature of the cells in a self-feeding loop. Keywords: fibroblast heterogeneity, host response, multiprotein arrays, peri-implantitis