Forty patients with active ulcerative colitis were randomly assigned to receive either 4 g of oral enterically coated 4-aminosalicylic acid (para-aminosalicylic acid) or placebo. The duration of treatment was 12 weeks. Disease activity was assessed by grading clinical symptoms of blood, mucus, urgency, sigmoidoscopic findings, and degree of histological inflammation in rectal biopsy specimens. At 12 weeks, 11 of 20 patients (55%) who received 4-aminosalicylic acid showed improvement in clinical and sigmoidoscopic variables. In contrast, only 1 of 20 patients (5%) who had received placebo showed improvement (P less than 0.005). Eighteen of the 19 patients in the placebo group who showed no improvement were treated subsequently with open-label 4-aminosalicylic acid. Of the 18, 11 showed clinical and sigmoidoscopic improvement. Patients allergic or intolerant to sulfasalazine with extensive disease were more likely to respond to 4-aminosalicylic acid.