Abstract: &#946;-Cyclodextrin (&#946;-CD) is a cage-like molecule consisting of seven glucose units and have appropriate size to form inclusion complexes with many hormones, vitamins and drugs. Due to having very poor aqueous solubility,&#946;-cyclodextrin is modified chemically for various applications. Experiments were conducted to examine effects of pre-hemolytic concentration of -cyclodextrin and its modified derivatives, methyl-&#946;-cyclodextrin (M&#946;-CD) and dimethyl-&#946;-cyclodextrin (DM&#946;-CD), on the osmotic fragility of dog and goat erythrocytes. Blood samples collected from healthy 10 dogs and 10 goats were analyzed within 5 h of collection. Erythrocyte suspensions were mixed with various concentrations of &#946;-CD, M&#946;-CD and DM&#946;-CD. The mixtures were then incubated for 30 min at 37&#deg;C and osmotic fragility of erythrocytes was measured. Incubation of all 3 Cyclo Dextrins (CDs) with erythrocyte suspensions of both species, dog and goat, induced a dose dependent increase in the erythrocyte osmotic fragility (p<0.01). The hemolytic effect was decreased in order DM&#946;-CD>M&#946;-CD>&#946;-CD. Hemolytic doses of these CDs were lower for goat erythrocytes than those of the dog erythrocytes. When &#946;-CD and its methylated derivatives are even used in pre-hemolytic concentrations, they might also reduce life span of erythrocytes. Due to importance of scientific knowledge on the cellular activity of cyclodextrins and growing number of its potential applications on diagnosis food preparations, our results may help to deal with the hemolytic activity of CDs for in vivo studies.