To investigate the biochemical parameters of the erythrocyte response to diamide-induced oxidative stress, alone or as adjuncts to serum values of CA-125 and human epididymal secretory protein E4 (HE4), in the diagnosis and study of endometriosis. University of Padova. Prospective study. Forty-five patients of reproductive age undergoing laparoscopy. All women were studied for endometriotic foci during laparoscopic surgery. Forty-one had laparoscopically and histologically confirmed endometriosis, and four did not. Twenty women with confirmed endometriosis were reassessed 1-4 months later. CA-125 and HE4 and two new parameters evaluated in erythrocytes after diamide-induced stress, that is, band 3 tyrosine phosphorylation (Tyr-P) level and decrease in total glutathione content (ΔGSH), were assessed in all patients. In association with serum CA-125 levels but not with HE4, diamide-related erythrocyte band 3 Tyr-P and ΔGSH were significantly higher in patients with endometriosis and were able to discriminate with high sensitivity and specificity between patients before and after surgery. Endometriosis is associated with an increase in systemic oxidative stress, affecting the antioxidative defenses of circulating erythrocytes. All related implications, including evaluation of other oxidative stress-related changes, warrant further study.