A series of thermodynamic studies on the mechanism of bacterial hemagglutination and on the inhibition of this reaction by mannose were carried out by the use of twin conduction microcalorimeter. Interaction between erythrocytes and aldoses used in the present study yielded practically no significant Q value. On the contrary, of the five aldoses tested, four aldoses (D-glucose, D-galactose, D-mannose and D xylose), the fifth being L-arabinose, were observed to yield exothermic heat by interaction with all strains of Shigella ftexneri, irrespective of the presence or absence of absence of fitnbriation. Of particular note, however, is that D-mannose reacted with the fimbriate strains, yielding a significant Q value qualitatively peculiar and characteristic of an exothermic interaction. Monosaccharide absorption studies on the cells of Sh. flexneri or on the red blood cells revealed that D-man nose was intensely absorbed by only the fimbriate strains of Sh. flexneri. The Q value yielded by the interaction between the non-fimbriate strain and mannose is of the exothermic type, whereas that observed by that between the fimbriate strain and mannose is conversely of the endothermic type. And the reaction of D-mannose with the purified fimbriae is characteristically of the endothermic type, and such was also true in the reaction system with the purified fimbriae and the erythrocytes. The fimbriate strains of Sh. flexneri reacted with mannan, polymer of mannose, to exhibit agglutination of the bacterial cells (Shigella-Mannan agglutination), yielding a Q value of the endothermic type, and this type of agglutination was intensely inhibited by D-mannose. It has been suggested from the results that the mannose molecule would be situated as the terminal sugar at the binding sites or receptor on the surface of the erythrocytes, and the fimbriac of the man nose sensitive type interact with this receptor.