PGE₂ and PGF_2α are known to act similarly in a number of animal tissues. They both facilitate regression of corpus luteum(Poyser, 1972; Fuch et al, 1974; Coudert et at, 1974) and stimulate contraction of uterine muscle (Laudanski et al, 1977; Porter et al, 1979; Hollingsworth et al, 1980). It is, however, not known whether these two prostaglandins exert similar actions in osmotic fragility of erythrocytes (Rasmussen et al, 1975) and PGF_2α alters conformation of membrane proteins (Meyers aud Swislocki, 1974). The former effect may not be mediated through changes in c- AMP concentration in the cell, since the adenylate cyclase activity in human erythrocyte is extremely low (Rodan et al, 1976; Sutherland et al, 1962) and the latter effect implies that physical state (or fluidity) of the membrane is altered by PGF_2α. The present study was undertaken to elucidate mechanisms of action of PGE² and PGF_2α on the human erythocyte membrane by examining their effects on osmotic fragility and Ca⁺⁺ binding to the membrane fragments. The results are summarized as follows: 1) PGE₂ and PGF_2α increased osmotic fragility at concentrations above 10^-11 M , the effect being similar for both hormones. The concentration of NaCl for 100% hemolysis was 1/16 ~ 1/17 M in the presence of 10^-11 M PGE₂ or PGF_2α and 1/18 M in the absence of the hormone (control). 2) When erythrocytes were suspended in 1/15 M NaCl solution, 44.2±4.3% of cells were hemolyzed. Addition of 10^-12 M PGE₂ or PGF_2α did not increase hemolysis. When the concentration of the hormones was increased to 10^-11 M , however the degree of hemolysis increased markealy to about 80%. No further increase in hemolysis was observed at concentration of the hormones above 10^-11 M . 3) The additional hemolysis due to 10^-11 M PGE₂ and PGF_2α appeared to he identical regardless of absence or presence of Ca⁺⁺ (0.5 ~ 10 mM) in the suspending medium. 4) In the absence of prostaglandin, the binding of Ca⁺⁺ to the erythrocyte membrane increased curvilinearly as the Ca⁺⁺ concentration increased up to 5 mM above which it leveled off. A similar dependence of Ca⁺⁺ binding on the Ca⁺⁺ concentration was observed in the presence of 10^-11 M PGE₂ or PGF_2α, however, the amount of Ca⁺⁺ bound at a given Ca⁺⁺ concentration was significantly higher than in the absence of the hormones. 5) As in the hemolysis, PGE₂ and PGF_2α did not affect the Ca⁺⁺ binding at a concentration of 10^-12 M , but increased it by about 100% at concentration above 10^-11 M . These result indicate that both tile osmotic fragility of erythrocyte and the Ca⁺⁺ binding to the erythrocyte membrane are similarly enhanced by PGE₂ and PGF_2α, but these two effects are not causally related. It is, therefore, concluded that the prostaglandin-induced hemolysis is not directly associated with alterations of the Ca⁺⁺ content in the membrane.