Patients with distal ulcerative colitis may be refractory to standard drug therapy. 5-Aminosalicylate, the active moiety of sulfasalazine, is effective topically in new onset distal colitis. Six patients with distal colitis unresponsive to sulfasalazine and corticosteroids had a prompt and dramatic response to the administration of 5-aminosalicylate enemas with clinical, sigmoidoscopic, and histological improvement. Topical 5-aminosalicylate should be a useful addition to the current available therapies for some patients with refractory distal ulcerative colitis.