There is currently considerable interest in the molecular modes of action of chemicals that induce cell fusion. This arises in part because of the continuing development of chemically-induced cell fusion as a laboratory tool. Thus poly(ethylene glycol), (PEG), has been used to fuse plant protoplasts [ 1,2] , bacterial protoplasts [3,4], plant protoplasts with animal cells [5-71, and animal cells in culture [8-l 21. The actions of chemical fusogens are also being investigated as a means of obtaining insights into the numerous instances of membrane fusion occurring in physiological and pathological systems in vivo [13,14]. To obtain information on the molecular mechanisms by which PEG induces the fusion of biological membranes we have studied: (i) The effectiveness of differing concentrations of PEGS (mol. wt 200-20 000) in causing LeschNyhan human skin fibroblasts to fuse; (ii) The state of water in these solutions by means of differential scanning calorimetry; (iii) The effect of PEG on the permeability of erythrocytes to 45Ca2+. Our observations indicate that PEG induces the fusion of fibroblasts by altering the physical state of bulk water adjacent to the cell surface and/or the water of hydration of the phospholipid polar groups in the cell membrane. Also, concentrated solutions of PEG act, in common with lipid-soluble fusogens, to allow Ca2’ to enter the cytoplasm of erythrocytes: this precedes the cell fusion reaction. It has been found, in addition, that PEG may be utilised in a controllable manner to induce fibroblasts to fuse by