Nitric oxide (NO) is generated from L-arginine by a family of enzymes called the NO synthases. Previous investigators have proposed that the expression of this inducible enzyme (iNOS) may account for the characteristic vasodilatation, oedema and impairment of get motility seen in active ulcerative colitis. Using a specific antibody to iNOS, we have investigated the distribution of this enzyme in colonic tissue from patients with histologically proven ulcerative colitis. Eight patients with ulcerative colitis expressed calcium-independent citrulline activity (9.96 +/- 2.34 pmol citrulline mg-1 protein min-1) and showed immunoreactivity to the iNOS antibody within the inflammatory infiltrate of the lamina propria, and also within the cytoplasm of the epithelial cells lining the colon. Five age-matched controls showed no calcium-independent citrulline activity (0.2 +/- 0.08 pmol citrulline mg-1 protein min-1) and no immunoreaction to the antibody. We conclude that this enzyme is present in colonic tissue including the epithelium from patients with active colitis. Inhibition of this enzyme may provide a novel therapeutic option for patients with active ulcerative colitis.