It was hypothesized that peri-implant tissue around loosening dental implants may contain cytokines with a potential to regulate osteoclasts. Peri-implant and/or gingival samples from loosened implants, chronic periodontitis (CP), and normal controls (n = 10 samples in each group) were analyzed using immunohistochemical staining to observe tumor necrosis factor alpha (TNF-α), interleukin 1-alpha (IL-1α), IL-6, platelet-derived growth factor A (PDGF-A), and transforming growth factor alpha (TGF-α). These cytokines were found in foreign-body giant cells, macrophages, fibroblasts, and epithelial cells. TNF-α, IL-1α, and IL-6 were increased (P .05; unpaired t test) in peri-implantitis and CP, whereas PDGF-A and TGF-α were not. In conclusion, cytokines with a potential to activate osteoclasts were found in both peri-implantitis and CP, but the cytokine profiles differed in that IL- 1α was the most prevalent cytokine in the former and TNF-α was the most common in the latter. These cytokines may contribute to peri-implant bone loss/loosening by stimulating formation and activity of osteoclasts and might be an amenable target for local therapies with cytokine modulators.