A facile systematic method which could be used to isolate proteins unique to transformed cells is under study. The procedure involves use of macromolecular reagents consisting of a) a reactive group capable of binding strongly to a specific protein or class of proteins; b) a macromolecular carrier; and c) a linkage between the two that is stable under normal physiological conditions, but which may be selectively broken. Reagents currently under study contain phenyl ester linkages which are stable under physiological conditions but can be broken quantitatively under conditions that do not result in reduction of disulfide bonds or oxidation of glycosol residues which are present in many proteins. Treatment for 10 min with 1 M hydroxylamine at pH 7, room temperature, results in complete cleavage of the phenyl ester linkages of the connector arm. The use of this approach to purify a trypsin-combining protein shown to be present in the mouse 3T3 cells is being studied. The biosynthesis of this protein in normal and transformed mouse cells is also under study.