In an effort to elucidate the cell surface molecules involved both in the adhesion of cells to their substratum and in the interaction of cytoskeletal elements with the surface membrane, a series of antisera have been produced which react with the cell surfaces. Two of these antisera induce reversible cell rounding and substrate detachment. The third has no effect on cell morphology or adhesion. An assay based upon the ability of membrane extracts to block the antibody induced rounding and detachment has been developed. Using this assay, membrane extracts will be fractionated and attempts made to purify the constituents which block the interaction of the immunoglobulin with the cells. Using the recently described methods for preparing immune-B-cell/plasmacytoma hybrids, monoclonal antibodies reactive with individual cell surface glycoproteins will be produced. These antibodies will be used for further structural, biochemical and genetic studies designed to understand the problems of cell adhesion and membrane-cytoskeletal interaction.