We are preparing a manuscript which describes our computer modeling of molecular packing modes in membranes of lipids containing docosahexaenoic acid (22:6 w3). Packing energies and lattice geometries were calculated for analogs of 18:0/22:6 diglycerides containing ester, ether, or vinyl ether linkages of the 1-position chain (diacyl, alkylacyl, plasmenyl glycerides). Surprisingly, the plasmenyl packings are more stable and compact than the diacyl and alkylacly ones. Disaturated reference models have somewhat more stable packings than polyunsaturated ones, but this is influenced greatly by the proportions of D and L optical isomers present. Provisional modeling parameters for phosphate containing head groups were tested. Steric factors in packing models containing all D-glycero lipids may require inversion of half of the head group conformations from their normal configuration. We will use synaptosomes to test experimentally whether polyunsaturated lipids pack in localized membrane domains, and whether plasmalogens are involved in membrane fusion or interaction with membrane proteins, as suggested by the modeling studies. We are setting up methods for isolating and purifying synaptosomes and their components from primate brain gray matter. Successive centrifugations on percoll and sucrose density gradients, combined with glycerol swelling and hypotonic lysis have proven effective in preparing whole synaptosomes, neurotransmitter vesicles, and plasma membrane domains.