Oxidative stress appears to play a role in the tissue damage of active ulcerative colitis, and it has been suggested that a defect in mucosal antioxidant defenses is a etiological factor in the disease. This study was undertaken to investigate the mucosal content and oxidation state of glutathione in ulcerative colitis in the active and inactive states and to examine the relationship between glutathione content and disease activity in this patient population. Endoscopic biopsies of colon mucosa were collected from normal subjects, from macroscopically normal tissue of patients with inactive and active ulcerative colitis, and from inflamed tissue of patients with active ulcerative colitis. The mucosal contents of GSH and GSSG were determined by liquid chromatography. We found no significant differences in tissue contents of reduced glutathione among the four groups. The median tissue level of oxidized glutathione in inflamed mucosa from patients with active ulcerative colitis was increased 1.7-fold (P = 0.017) over that of patients with inactive disease. The oxidized glutathione content of the mucosa also showed significant positive correlations with clinical and histological indices of disease severity among ulcerative colitis patients. In conclusion, a change in the redox status of mucosal glutathione is associated with inflammation and disease activity in ulcerative colitis. This change appears to be a consequence of inflammation rather than a pathogenic factor for the disease.