Summary:An increased destruction of red cells was previously demonstrated during experimental fever. The present study deals with the changes in red cells produced by extended exposure in vitro to temperatures in the biological range of fever.By elevating the temperature only a few degrees above normal body temperature a distinct increase in spontaneous haemolysis and osmotic fragility of rabbit red cells was observed. By combination of exposure to heat in vitro and survival‐studies in vivo, using red cells labelled with 51Cr or 59Fe, it was confirmed that even small elevations of temperature greatly reduced the survival of the red cells in the circulation. In a supplementary investigation in rabbits a significant increase in osmotic fragility was observed during experimentally produced fever using injections of bacterial pyrogen or external heating.No difference in glucose consumption during incubation of red cells in vitro at normal and elevated temperature could be demonstrated and inactivation of vital enzymes seems not to be responsible for the injury to the cells. Other mechanisms, especially the possibility of changes in the lipoprotein structure of the cell membranes, are discussed.In a single study, human red cells exhibited the same vulnerability as rabbit red cells to small elevations of temperature, although their sensitivity was less.