Human erythrocytes (RBC) were incubated for various time at 37 °C in hypertonic solutio,ts of NaCl (1.5 M) or sucrose (1.2 M) and then rehydrated in isotonic NaCl or sucrose media in the presence or absence of divalent cations Ca²⁺ and Zn²⁺. After equilibration in hypertonic sucrose both cations significantly increased the extent of hemolysis at concentration dependent manner, but show more complex response after equilibration in hypertonic NaCl media. In thin case both Ca²⁺ and Zn²⁺ ions lose their activation ability during rehydration in isotonic NaCl media, and Ca²⁺ did so in isotonic sucrose. Dehydration of cells in hypertonic sucrose solutions in the presence of 100 mM of cations Na⁺, K⁺ and Mg²⁺ leads to decrease the extent of lysis after rehydration but dues not influence activation ability of Ca²⁺ and Zn²⁺, whereas addition of Ca²⁺ to hypertonic sucrose solution completely abolishes activation effect of both ions. The model of posthypertonic lysis is presented according to which action of cations Ca²⁺ and Zn²⁺ may be explained by their specific binding to activatory and inhibitory membrane sites, regulating membrane permeability during reswelling from hypertonic salines.