1. Rectal dialysis in vivo was used to assess rectal mucosal release of histamine in patients with ulcerative colitis and in control subjects. 2. Rectal mucosal histamine release was significantly increased in ulcerative colitis, whether the patients were in remission or relapse. The highest values were found in active colitis, but in several such patients histamine release was within the control range. Measurement of rectal mucosal electrical potential difference suggested that increased mucosal histamine release in this group of patients was not due to enhanced epithelial permeability. 3. Rectal dialysis appears to be a useful method for assessing mucosal histamine production and the results obtained are consistent with the hypothesis that immediate hypersensitivity reactions could be of importance in some patients with ulcerative colitis.