Sickle cell trait subjects are potentially at risk with microvascular complications frequently associated with high altitude and extreme exertion. Studies conducted in our laboratory suggest that exposure of sickle cell trait subjects to treadmill exercise resulted in an increase not only in the susceptibility of red blood cells to oxidation but also in the density of RBC membrane. The trend of increased susceptibility of red cells to oxidation as a consequence of exercise was associated with relatively excessive production of H2O2, inefficient breakdown of H2O2 by GSH-Px- and catalase-catalyzed reactions, and inability/failure to show a transitory increase in the activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-generating enzymes.