Incubation of normal erythrocytes with 10 mM H
_{2}
O
_{2}
has caused a loss of deformability. This loss of deformability was correlated with the extent of malonyldialdehyde, MDA (an indicator of lipid peroxidation) and alanine production (an indicator of protein degradation). The susceptibility of erythrocytes from 21 non‐insulin‐dependent diabetes mellitus (NIDDM) and 18 hemodialysis patients, 21 cigarette smokers and 25 healthy controls to in vitro oxidative stress with H
_{2}
O
_{2}
has been measured as MDA production. Besides this, their erythrocytes reduced glutathione (GSH; an antioxidant) level has also been determined, but before exposure to H
_{2}
O
_{2}
. Erythrocytes from NIDDM and hemodialysis patients have shown significant increase in MDA production and a significantly low GSH level, compared to healthy controls. In cigarette smokers, although the GSH level was significantly low, but there was no significant difference in MDA production, compared to healthy controls. The low GSH level in NIDDM and hemodialysis patients, and smokers indicates that their erythrocytes were exposed to oxidative stress (an increase in free radical load) in vivo, resulting in an overconsumption and/or decreased production of GSH. The increased susceptibility to oxidative stress along with the decrease in some antioxidants (e.g., GSH) may explain the significant increase in MDA production in NIDDM and hemodialysis patients. But in cigarette smokers, the increased susceptibility to oxidative stress is probably not sufficient to cause a significant increase in MDA production. The results may also indicate an increased susceptibility to the loss of erythrocyte deformability in NIDDM and hemodialysis patients compared to healthy controls.