Transforming growth factor alpha (TGF alpha) is not only a potent mitogen for several cell types, it interferes with cell differentiation. To investigate the possible role of TGF alpha in the fusion of the palatal processes in humans, the distribution of TGF alpha and its receptor (epidermal growth factor receptor = EGF-R) were studied using immunohistochemistry. 23 human palates were obtained from embryos and fetuses at 6 to 12 weeks of gestation and embedded in paraffin. In each case, the degree of cell proliferation was assessed using an antibody reacting with the nuclear antigen Ki-67. The epithelial and mesenchymal cell phenotypes were studied with anti-cytokeratin and anti-vimentin antibodies. TGF alpha and its receptor were detected in all the human palates, regardless of the stage of fusion. They were more highly expressed in the epithelial cells than in the mesenchymal cells of the palatal shelves. At first, proliferative activity was intense in both the mesenchyme and the epithelia and was later principally limited to the nasal or oral epithelia and also to the degenerating epithelial seam. At 10 weeks, when the midline palatal seam broke up into epithelial islands, the epithelial cells remained immunolabeled for TGF alpha, EGF-R and showed an increased number of proliferating cells. Programmed cell death (PCD) of medial edge epithelia (MEE) has been well documented, however other mechanisms must be considered during palatogenesis. Complex interactions between different growth factors have a probable role in epithelial mesenchymal transformation (EMT) and migration as well as in extracellular matrix synthesis.