The mechanisms of membrane assembly, and the conditions which influence membrane stability in normal and diseased cells are the principal focus of this program. We have previously reported that cell membranes assemble and are optimally stable at a critical temperature Tp, the physiological temperature of the cell; the lipid composition of the membrane bilayer is the principal determinant of the critical temperature. The conditions for membrane assembly and stability may be simulated in aqueous dispersions of the total lipid extracts of membranes. Thus, for normal, disease-free cells the critical temperatures measured in these aqueous dispersions have been shown to equal Tp. A rapid technique for this measurement has been developed and applied to the total membrane lipid extracts from human erythrocytes (37.2 degrees C), rat spinal cord and cerebrum (39.0 degrees C), rabbit erythrocytes (39.0 degrees C) and cerebellum (39.4 degrees C), in general agreement with reported values for Tp. Destabilization of cell membranes, and membrane breakdown may occur when the lipid composition is altered by metabolism such that the critical temperature of the membrane is less than Tp. This concept has been utilized to identify a lipid defect that is site-specific in post-mortem brain samples from patients with Alzheimer's disease. The defect is manifested as a deficit in ethanolamine plasmalogen in mid-temporal cortex with marked neurodegeneration, in contrast to normal values in regions that are disease-free.