Dipeptidyl peptidase (DPP) II and IV activities were demonstrated in unfixed cryostat sections of gingival tissue from chronic periodontitis patients using histochemistry with 2-methoxy-4-naphthylamine (MNA) substrates. In the case of DPP IV, enzyme localization was confirmed by immunocytochemistry with mouse monoclonal antihuman DPP IV (CD26) antibody. Inflammatory cells containing enzyme were identified in adjacent sections with mouse monoclonal antibodies directed against leukocyte differentiation antigens. Lys-Ala-MNA and Ala-Pro-MNA staining in acid buffer for DPP II was only found in a few fibroblasts in superficial tissue. Staining with Gly-Pro-MNA and Ala-Pro-MNA in alkaline buffer for DPP IV was localized in some CD4 and CD8 positive T lymphocytes, CD68 positive macrophages, and fibroblasts and these cells also reacted with the enzyme antibody. DPP IV-containing macrophages and T lymphocytes were seen in the epithelium. In deeper granulomatous tissue Gram positive and negative bacteria stained with the histochemical substrates, but not the DPP IV antibody. Fibroblast DPP II and IV might participate in cellular interactions with collagen, while T lymphocyte DPP IV may be involved in cell signalling.