A line of homozygous transgenic mice (TG.AC) carrying a v-Ha-ras gene fused to the promoter of the zeta globin gene produces a variety of mesenchymal and epithelial neoplasms including odontogenic tumours. The 1-year incidence of odontogenic tumour formation in these mice was approx. 35%. Tumours formed more often in the mandible than maxilla. The various types of tumours frequently presented with: (1) primarily mesenchymal cells in a dense fibrous-like matrix, or (2) loose stroma surrounded by anastomosing cords of epithelial cells that exhibited squamous differentiation, or (3) odontomas forming mineralized tooth structures by well-differentiated odontoblasts and ameloblasts. Some tumours had areas with all three of these characteristics. Mineralized dentine and enamel in the odontomas were morphologically similar to those of normal murine teeth. Odontogenic tumours expressed the v-Ha-ras transgene that was primarily localized to the mesenchymal cells. Proliferating-cell nuclear antigen immunohistochemistry showed that the mesenchymal cells adjacent to the epithelial cords not only expressed the ras transgene but were also actively proliferating. The TG.AC mouse provides an excellent model for the study of odontogenic tumours and tooth development.