The effect of glucose and galactose on the membrane deformability of red blood cells (RBC) suspended in isotonic solution was determined using micropipette aspiration technique. In this method, a negative pressure was applied to the RBC membrane via a micropipette and the resulting deformation was analyzed using a Kelvin model to yield a membrane elastic modulus E. When glucose concentration was increased from 0 to 0.3 M/dm3 in the extracellular media, E increased seven-fold (p less than 0.0001) with most increase occurring in the 0-0.05 M/dm3 range. The increase in E due to glucose was not completely reversible. The time constant of increase in E was about 14 minutes. Whereas, galactose had no significant effect on the membrane elasticity up to a concentration of 0.3 M/dm3. Increase in the RBC membrane rigidity in the presence of glucose may be due to binding of glucose to the membrane and intracellular proteins. The results obtained may be important for explanation of decrease in tumor blood flow during hyperglycemia.