The objective of this study was to investigate photodynamic therapy (PDT), using blue dye and red light, for prophylaxis and treatment of cutaneous Candida albicans infections in mice. A mouse model of skin abrasion infected with C. albicans was developed by inoculating wounds measuring 1.2 cm by 1.2 cm with 10(6) or 10(7) CFU. The use of a luciferase-expressing strain of C. albicans allowed real-time monitoring of the extent of infection in mice noninvasively through bioluminescence imaging. The phenothiazinium salts toluidine blue O (TBO), methylene blue (MB), and new methylene blue (NMB) were compared as photosensitizers (PS) for the photodynamic inactivation of C. albicans in vitro. PDT in vivo was initiated either at 30 min or at 24 h after fungal inoculation to investigate the efficacies of PDT for both prophylaxis and treatment of infections. Light at 635 ± 15 nm or 660 ± 15 nm was delivered with a light dose of 78 J/cm(2) (for PDT at 30 min postinfection) or 120 J/cm(2) (for PDT at 24 h postinfection) in multiple exposures with bioluminescence imaging taking place after each exposure of light. In vitro studies showed that NMB was superior to TBO and MB as the PS in the photodynamic inactivation of C. albicans. The efficacy of PDT was related to the ratio of PS concentration to fungal cell density. PDT in vivo initiated either at 30 min or at 24 h postinfection significantly reduced C. albicans burden in the infected mouse skin abrasion wounds. These data suggest that PDT is a viable approach for prophylaxis and treatment of cutaneous C. albicans infections.