The term colitis suggests mucosal inflammation as the key event. However, it may be that the disease starts with mucosal hyperproliferation, and inflammation of the impaired mucosa is a succeeding event. Therefore we studied the activity of the intestinal diamine oxidase (DAO) in ulcerative colitis (UC). This enzyme was shown to have a mucosal antiproliferative function. Biopsy specimens of 30 patients having a normal rectosigmoidal mucosa showed a DAO activity of 22.8 nmol/min g. In 12 UC patients the DAO activity was 2.7 nmol/min g (p = 0.01). In 3 patients where UC was in remission the DAO activity was 103, 107 and 208 nmol/min g, indicating an antiproliferative rebound effect. Together with the strongly reduced monoamine oxidase (MAO) activity, the decrease in DAO activity indicates that the large bowel in UC is unable to produce a proliferation terminating substance (probably gamma-aminobutyrate) derived from polyamine metabolism by oxidative deamination (DAO) or by the interconversion pathway (MAO).