We have studied the spontaneous formation of giant liposome from dry lipid film under an aqueous solution of long DNA molecules, T4DNA 165 kbp. The number density of DNAs entrapped inside liposomes formed with 10 mM Mg2+ solution is one order of magnitude higher than that in the bulk solution. In addition, DNA molecules assume a somewhat shrunken conformation in phospholipid solution containing Mg2+. The mechanism of the enhanced uptake of DNA into cell-sized liposomes is discussed in relation to the local increase in osmotic pressure due to DNA molecules attached to the membrane surface through Mg2+. (C) 2003 Elsevier B.V. All rights reserved.