The organotypic raft culture model has been shown to be a useful method for examining the effects of biochemical manipulation on various epithelial cell types, using in vitro conditions that simulate the in vivo environment of the tissue of origin. To investigate this method as a model for photodynamic therapy (PDT), we cultures the oral squamous carcinoma cell line YD-10B on fibroblast-containing collagen gels at the air-liquid interface and assessed the efficacy of PDT using a photosensitiser 5-ALA-hexenyl ester. PDT effect on YD-10B organotypic raft cultures after twenty- four hours was determined. The number of residual cells was significantly reduced in comparison to control at all four different conditions. PCNA immunostaining and TUNEL assay revealed that PDT inhibited cell proliferation and increased apoptosis. These findings suggest that the organotypic raft culture model provides an effective and rapid laboratory method of investigating strategies for PDT on oral precancerous lesions and squamous cell carcinomas