In an investigation of endogenous regulation of epithelial interaction, it was found that cultured embryo fibroblasts release an activity which causes loss of junctional attachment and separation of contiguous epithelial cells. This activity was originally observed in freshly cultured human mammary cells, but the MDCK cell line is also sensitive and has been used to develop an assay of activity. The activity is due to a protein that is heat-labile and sensitive to reducing agents and has a relative molecular mass of approximately 50,000 by gel filtration in the presence of 6 M-guanidinium hydrochloride or 8 M-urea. We term the agent 'epithelial scatter factor'. It is not known whether the factor acts directly or indirectly on junctional components. Besides its effect on cell relationships, the factor causes a change in cell morphology and local movement. In investigations so far, the scatter factor has been released only by fibroblasts of embryonic origin. Some but not all epithelial cells are sensitive; other cell types are not. The factor may be involved in morphogenetic changes involving the epithelium in embryonic or adult life. There is as yet no evidence for a role in the spread of tumour cells.