Trehalose has been shown to play a role in osmotolerance or desiccation tolerance in some microorganisms, anhydrobiotic invertebrates and resurrection plants. To test whether trehalose could improve stress responses of higher eukaryotes, a mouse cell line was genetically engineered to express bacterial trehalose synthase genes. We report that the resulting levels of intracellular trehalose (similar to 80 mM) are able to confer increased resistance to the partial dehydration resulting from hypertonic stress, but do not enable survival of complete desiccation due to air drying. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V, All rights reserved.