The cryoprotective effects of various additives such as saccharides and polyalcohols on sonicated liposomes during freeze-drying were investigated. Fusion of liposomes was measured as energy transfer and size distribution. There was considerable difference among the additives in their cryoprotective ability. Polyalcohol systems showed considerable fusion. Although monosaccharides completely prevented the fusion of liposomes during freeze-drying similarly to disaccharides, they showed far less ability to retain the entrapped calcein of liposomes than disaccharides. The heating thermograms of differential scanning calorimetry of dipalmitoylphosphatidylcholine (DPPC) in the state of sonicated liposomes freeze-dried with various additives were measured. Disaccharides and monosaccharides again markedly differed in their effects on the thermal property of the DPPC. The reason for the variety in their cryoprotective ability was attributed to the difference in the strength of their interaction with phospholipid head group.