Two human sera with antibodies against smooth muscle were used to investigate the distribution of actin in moving oral epithelial cells by immunocytochemical methods. Epithelial outgrowths from explants of rat and human oral mucosa showed a constant positive staining in the peripheral parts of the marginal cells but not in the more central parts of the epithelial sheet. This is in agreement with theories of the importance of the marginal cells in the migratory behavior of the epithelial outgrowth. Subcultured epithelial cells from the human explants showed positive staining of fine fibers in the cytoplasm. During healing of experimental oral wounds from humans and monkeys actin fibers could be demonstrated in only one of 18 cases in the epithelial cells adjacent to the wound, though positive staining of various cells was seen in the underlying tissue. This is in contrast to the evidence presented in previous studies of cells taking part in the re-epithelialization process.