Abstract: Background: Aminothiols have a critical function as intracellular redox buffers and constitute furthermore an important extracellular redox system. Lipid peroxidation is increased in chronic heart failure (CHF), but the contribution of each thiol to oxidative stress in this syndrome has not been evaluated. Aim: To assess the correlation between blood and plasma concentrations of aminothiols and lipid peroxidation as marker of oxidative stress in CHF patients. Methods: Blood reduced glutathione (GSH), plasma total and reduced cysteine, cysteinylglycine, homocysteine, GSH, alpha-tocopherol, ascorbic acid, and free malondialdehyde (MDA) were assessed in samples obtained from 26 CHF heart transplant candidates and 26 age- and gender-matched controls with atherosclerotic risk factors and no history of cardiovascular disease. Results are expressed as median and interquartile range (I-III). Results: MDA levels were significantly higher in CHF patients than in controls [1.03 (0.56-1.60) mu M vs. 0.70 (0.40-0.83) mu M, p = 0.006]. Blood reduced GSH concentrations were significantly higher [662 (327-867) mu M vs. 416 (248-571) mu M, p = 0.016], while alpha-tocopherol levels were significantly lower [15 (13-19) mu M vs. 21 (17-32) mu M, p = 0.001] in CHF patients than in controls. By multivariate logistic regression analysis, the only independent predictors of lipid peroxidation, as expressed by NIDA levels >= 1.00 mu M, were increased blood GSH concentrations (OR 1.003 per unit, 95% CI 1.001 to 1.006, p = 0.008), ischemic (OR 20, 95% CI 2.6 to 155, p = 0.004) and non ischemic CHF etiology (OR 11, 95% CI 1.3 to 99, p = 0.026). Conclusions: Abnormalities in intracellular GSH cycling are associated to increased lipid peroxidation in CHF.