It is postulated that an enhanced production of nitric oxide by inflamed intestine plays a role in the pathophysiology of active inflammatory bowel disease. In this study, systemic NOx concentrations and colonic nitric oxide synthase activity were determined in patients with ulcerative colitis or Crohn's disease. The relationship between these two parameters and disease activity, as well as differences in nitric oxide synthase activity between ulcerative colitis and Crohn's disease, were areas of specific focus. Patients with active ulcerative colitis and Crohn's disease had significantly elevated plasma NOx concentrations; a positive correlation was found between NOx values and inducible nitric oxide synthase activities in the active mucosa of these patients. In active ulcerative colitis, levels of inducible nitric oxide synthase were significantly elevated in both normal and inflamed mucosa, although inducible nitric oxide synthase activity was higher in the latter. These colonic inducible nitric oxide synthase activities correlated well with the results of endoscopic and histologic grading of inflammation. There was no increase in constitutive nitric oxide synthase activity in patients with active ulcerative colitis. However, constitutive nitric oxide synthase activity was significantly increased in the inflamed mucosa in patients with Crohn's disease. In Crohn's disease, elevated inducible nitric oxide synthase activity was found in both normal and inflamed mucosa, with no significant difference between the tissues. Such differences in nitric oxide production in the colonic mucosa possibly reflect the significant differences in the pathophysiology and characteristic clinical features between ulcerative colitis and Crohn's disease.