Investigations on the dose response of cell fusion, induced by ionfree aqueous polyethylene glycol (PEG) solutions, reveal distinct lowest fusogenic PEG concentrations for different permanently growing mammalian cell lines. Part o f the requisite PEG can be replaced by carbo hydrates, preserving the fusogenity o f the solutions. This discriminates two effects o f PEG solutions causing cell fusion: a) cell shrinkage, the required hyperosmolality o f the solutions may be provided by PEG or by carbohydrates, is supposed to cause intracellular processes necessary for consolidating polycaryons; b) membrane alterations, which can not be induced by carbo hydrates, enable intimate cell-cell contact via particle-free membrane areas. Depending on cell line salts can not only raise the osmolality o f PEG solutions but are able to co-operate with PEG in generating membrane alterations.The polyethylene glycol-(PEG)-induced cell-cell fusion, as many other fusion events, consist of several distinct stages: (a) cells come to very close proximity, their adjacent membranes contact via particle-free lipid areas, (b) intercellular cytoplasm atic bridges develop at these contact sites and (c) the cytoplasm atic bridges expand and stable condi tions in m em brane and cytoplasma of the poly caryons are restored (for ref. see [1,2]). By which properties o f PEG solutions the necessary cell altera tions are induced was still an open question [1,3]. In this paper I demonstrate, how in ionfree fusogenic PEG solutions PEG can be replaced in part by carbohydrates an d /o r salts. These findings discrim i nate at least two properties of PEG solutions neces sary for cell fusion. There is evidence that one of them accounts for mem brane alterations enabling intim ate cell-cell contact via particle-free lipid areas whereas the other induces intracellular processes involved in consolidating polycaryons. The high affinity o f PEG molecules to water is supposed to be basicly responsible for all fusogenic properties of aqueous PEG solutions.C onfluent monolayers of permanently growing m am m alian cell lines (HeLa, HE, BT5C1, B IC R / M 1R-K) were used in standardized fusion experi ments carried out at first with ionfree aqueous PEG solutions [2]. Cytotoxic effects rem ained negligible in all experim ents presented. The fusion yield ex