To determine the influence of inflammation and topical treatment with 5-aminosalicylic acid or prednisolone on arachidonic acid metabolism in vivo, we carried out a double-blind controlled study on the release of prostaglandin E2 and leukotriene B4 to the rectal lumen in 24 consecutive patients with proven distally located ulcerative colitis. Before and at days 15 and 29 a dialysis bag was placed in the emptied rectum for 4 h prior to assessing clinical, endoscopic, and histologic disease activity. A single enema was given daily at bedtime (1 g 5-aminosalicylic acid or 25 mg prednisolone) until complete remission or for a maximum of 4 wk. Clinical and endoscopic remission was obtained in 16 (7 on 5-aminosalicylic acid) and 11 (3 on 5-aminosalicylic acid) patients, respectively. Luminal concentrations of prostaglandin E2 and leukotriene B4 were positively correlated to disease activity and significantly decreased among the prednisolone-treated patients. In both treatment groups a decrease toward normal levels occurred in patients responding to therapy. In retrospect, the pretreatment prostaglandin E2 and leukotriene B4 levels were significantly higher in patients not responding to therapy than in those improving during treatment. In conclusion, luminal prostaglandin E2 and leukotriene B4 levels may prove more useful predictors of the outcome of treatment in relapsing ulcerative colitis than clinical indices of disease activity.