Nitric oxide (NO) is produced in tissues by NO synthase with the liberation of equimolar amounts of citrulline. Citrulline concentrations were significantly higher in rectal biopsy specimens from patients with active ulcerative colitis than in those from patients with quiescent disease or with normal histology. Incubation of biopsy samples from patients with ulcerative colitis with NG-monomethyl-L-arginine (L-NMMA) inhibited citrulline production. These findings suggest that mucosal NO biosynthesis is increased in active colitis and that NO may have a pathogenic role in ulcerative colitis.