OBJECTIVE - To assess the effect of acute physical exercise on oxidative stress and glutathione redox status and the relation to physical fitness in otherwise healthy young men with IDDM. RESEARCH DESIGN AND METHODS - Nine men with IDDM (HbA(1c) 7.3 +/- 1.7%), ages 21-30 years, and 13 matched control subjects exercised on a bicycle ergometer for 40 min at 60% of their maximal oxygen consumption (Vo(2max)). Oxidative stress was assessed with plasma thiobarbituric acid reactive substance (TEARS) levels (an index oi lipid peroxidation) and, in response to exercise, also glutathione redox status. For glutathione redox status, blood total glutathione (TGSH) and oxidized glutathione (GSSG) were determined. Blood samples were drawn immediately before and alter exercise. RESULTS - Resting plasma TEARS levels were markedly elevated in diabetic patients (2.2 +/- 0.7 vs. 0.9 +/- 0.4 mu mol/l; P = 0.0002), Mean blood TGSH was higher in diabetic subjects (1,203 +/- 221 vs. 936 +/- 156 mmol/l; P = 0.002), with no significant difference in GSSG or GSSG/TGSH values. Exercise increased plasma TEARS and blood GSSG by similar to 50% in both groups. Resting plasma TEARS had a strong inverse correlation (r = -0.82; P = 0.006), and the exercise-induced percentage increase in TEARS had a strong positive correlation (r = 0.81), P = 0.008) with VO2max in diabetic subjects only. CONCLUSIONS - Glutathione redox status appears to be adequate in healthy young moderately active diabetic men. On the other hand, they demonstrated increased resting and postexercise oxidative stress as indicated by plasma TEARS. Although exercise acutely induces oxidative stress, in patients with diabetes, physical fitness may have a protective effect against oxidative stress.