D ysregulation of TGF beta 2, a modulator of cell growth and differentiation, can result in uncontrolled growth and tumor formation. Our comparative studies on the expression of TGF beta 2 mRNA and protein indicate that TGF beta 2 may primarily be a regulator of epithelial differentiation during tooth development (between 13 and 20 gestational wk) and tumorigenesis of odontogenic neoplasms. A paracrine mode of action for TGF beta 2 in early human tooth germ (cap/early bell stage) is suggested by location of mRNA in the mesenchyme surrounding the tooth germ, whereas protein is found in the epithelial dental lamina and enamel organ. During the late bell stage, TGF beta 2 gene expression shifted from the mesenchyme to the odontogenic epithelium and was colocalized with protein, suggesting an autocrine role for the terminal differentiation of ameloblasts. In odontogenic tumors of epithelial origin (ameloblastomas) and epithelial-ectomesencymal origin (ameloblastic fibromas), TGF beta 2 mRNA was mostly located in the mesenchymal tumor component and protein in the epithelial tumor component. Odontogenic ectomesenchymal tumors (myxomas) were not associated with TGF beta 2 mRNA and protein expression. The results imply that TGF beta 2 may play an important role in epithelial-mesenchymal interactions in human tooth morphogenesis and development of odontogenic tumors.