This study was planned to determine the effects of free-radical-induced damage on the Na+,K+-ATPase activity of erythrocytes during hyperthyroidism and 4 wk after propylthiouracil ( PTU) therapy (400 mg/d). The levels of plasma thiobarbituric acid-reactive substances (TBARS) as a marker of lipid peroxidation, erythrocyte glutathione ( GSH) concentration as an antioxidant, blood ATP concentration, and erythrocyte membrane Na+,K+-ATPase activity were determined in female hyperthyroid patients ( n = 22, mean age 40.5 +/-6.5 yr). Before the PTU therapy, plasma TBARS concentration was significantly higher and the levels of blood ATP and erythrocyte GSH and the activity of membrane Na+,K-(+)-ATPase were significantly lower in the hyperthyroid patients ( n = 15 women, mean age 40.8 +/-7.3 yr). Four weeks after PTU therapy, plasma TBARS concentration was decreased, and levels of erythrocyte GSH and blood ATP and of Na+,K+-ATPase activity of erythrocytes were elevated in the treated patients. There was a significant positive correlation between blood ATP concentration and Na+,K+-ATPase activity, and a negative correlation between plasma TBARS concentration and Na+,K+-ATPase activity before PTU. Our results might help to clarify the effects of the oxidative mechanisms on the erythrocyte membrane Na+,K+-ATPase activity in hyperthyroid patients.