Calcium channel blockers (nifedipine, verapamil, diltiazem), calmodulin antagonists (trifluoperazine, calmidazolium, compound 48/80) and anti-free radical agents (allopurinol, desferrioxamine, mannitol, L-methionine) were tested for their potency to stabilize human erythrocytes against hypotonic hemolysis. The anti-free radical agents and compound 48/80 did not confer the membrane stabilization. Nifedipine, verapamil, diltiazem, calmidazolium and trifluoperazine at low concentrations, protected the cells from the hypotonic hemolysis while at higher concentrations they caused lysis. Similar biphasic changes were produced by the detergents sodium dodecyl sulphate (SDS) and Triton X-100. The drug concentration-dependency of the biphasic changes in the erythrocytes osmotic fragility produced by calcium channel blockers and calmodulin antagonists was not affected by low concentrations of SDS and Triton X-100. On the other hand, these drugs did not prevent the hemolysis produced by high concentrations of the detergents. The above as well as the observation that the membrane stabilization is conferred only by relatively high concentrations of calcium channel blockers and calmodulin antagonists suggest that membrane stabilization is not responsible for anti-ischemic effects of these agents reported in the literature.