ABSTRACT The action of temperatures above 48° C. on the red cell is usually regarded as a classical example of the irreversible effects of injury, the lysis which follows being attributed to a surface membrane becoming permeable because its lipid components are melted or because its protein components become denatured. Recently it has been found that the effects are considerably more complex, and increasing emphasis is being placed on the role which fragmentation plays in the phenomenon of heat haemolysis. Ham, Shen, Fleming & Castle (1948) have pointed out that the fragmentation which precedes haemolysis results in the cells of the system becoming more and more spherical, so that the extent to which each cell can swell before its surface is stretched becomes less and less, and the tonicity in which it haemolyses becomes greater and greater; when there is sufficient fragmentation, indeed, human red cells will haemolyse even in an isotonic medium such as plasma. The tonicityvolume relations of cells which have lost one or more of these fragments during heating to temperatures in the neighbourhood of 48° C., however, are substantially the same as those of intact cells (Ponder, 1948a), and both cells and fragments show substantially the same resistance to haemolysis by saponin and by digitonin; these observations point to the osmotic properties and the properties which determine the resistance to lysins being shared by cell and fragment, and to the unit structure upon the integrity of which these properties depend being smaller than the intact red cell. The possibility that this is so suggests that something may be learned by examining the shape of the red cells and fragments more closely, since the ability to maintain shape and to undergo shape transformations are also properties which are usually thought of as associated with the red cell as a unit structure.