The surface properties of cells may be very important in relation to abnormalities of cell-cell interaction, such as the loss of contact inhibition, decreased cell adhesiveness, and the tendency to metastasis seen in neoplastic tissue. Phospholipids are important structural components of cellular membrane surfaces. This study proposes to: (1) Determine the phospholipid content and composition of subcellular membrane fractions from a variety of human tumors. (2) Determine the mechanism whereby cardiolipin localization becomes grossly distorted in hepatomas (and possibly in other cancers). (3) Test the hypothesis that primary alterations in membrane phospholipids caused by malignant transformation result in secondary changes in the activity of membrane-bound, phospholipid- requiring enzymes. Projects (1) and (2) have not been previously investigated and are of considerable interest because of (a) the possible relationship of phospholipid abnormalities to cell surface properties, (b) as basic problems in biology, and (c) relative to the problem of disturbed biogenesis of membranes in neoplasia. Project (3) involves the testing of a unique hypothesis which could elucidate important secondary mechanisms of the control of enzyme activity in tumors.