Our previous in vitro study has shown that toluidine blue (TB)-mediated lethal photosensitization of periodontal pathogens (PPs) from periodontal patients is possible. The purpose of this study was to investigate whether TB-mediated photosensitization exerted damaging effects on periodontal tissues in mice. Twenty-four mice were randomly divided into four groups; the experimental photodynamic therapy (PDT) group was treated with 1 mg/ml TB and light irradiation (60 J/cm(2), 635 nm, 337 s). Those in control groups were subjected to 140 J/cm(2) laser irradiation alone or to 2.5 mg/ml TB alone or received neither TB nor light exposure. All the mice were killed 72 h after they had been subjected to PDT, and periodontal tissue samples were taken for histological examination. During the 72 h observation period, no mice showed any distress. No necrotic or inflammatory changes were found in the gingiva, dentin, dental pulp or alveolar bone of the mice in any of the groups in this study. The results suggest that TB-mediated PDT is a safe antimicrobial approach for the treatment of periodontopathy without damaging effects to adjacent normal tissues.