Iron overload was developed in rats by ip injection of iron-dextran. Iron concentration in plasma increased 12-fold after 20 h of iron supplementation and unsaturated iron binding capacity (UIBC) drastically decreased in iron overloaded compared to control rats (69 +/- 36 and 177 +/- 19 micrograms/dl, respectively). Lipid peroxidation in plasma increased by 285% and plasma alpha-tocopherol content decreased by 40% after 20 h of iron overload. alpha-Tocopherol supplementation decreased by 30% the measured increase in TBARS content in plasma after iron injection. On the other hand, both iron and TBARS content in erythrocytes were not significantly different in control and iron loaded rats. However, red blood cells from iron treated rats exposed to pro-oxidant conditions showed a significant increase in TBARS content as compared to control erythrocytes. alpha-Tocopherol pretreatment prevented this increase. Moreover, red blood cells from iron loaded rats showed a higher content of TBARS after incubation with plasma from iron-dextran injected rats than after incubation with plasma from control animals. This measured increase was partially prevented by alpha-tocopherol supplementation. Neither the activity of antioxidant enzymes nor the content of alpha-tocopherol in red blood cells were affected by iron overload. Total thiols content was significantly lower (30%) in erythrocytes isolated from iron treated rats. The data presented here suggest that free radical generation catalyzed by metal ions may lead to consumption of thiols. The decrease in thiols content in erythrocytes could afford an appropriate degree of protection and avoid other oxidative damage to these cells.