Excessive nitric oxide (NO) production by an isoform of NO synthase that can be induced by inflammatory stimuli leads to changes in vascular permeability and to tissue injury. We measured NO synthase activities in mucosa and muscle from the colons of control patients (n = 11) and patients with ulcerative colitis (6) or Crohn's disease (4). NO synthase activity in colonic mucosa of ulcerative colitis patients was 0.55 (median interquartile range 0.32-0.57) nmol/min per g tissue, which was about eightfold higher than the value in control mucosa, with no individual overlap (p < 0.001). With colonic muscle there was no difference in NO synthase activity between ulcerative colitis patients and controls. In the patients with Crohn's disease, mucosal NO synthase activity did not differ from control values and activity in the colonic muscle was low. Thus, induction of colonic NO synthase may be involved in the mucosal vasodilation and increased vascular permeability of active ulcerative colitis, and could also contribute to the impaired motility that accompanies toxic dilation.