To investigate the efficacy of azathioprine in treating patients with severe ulcerative colitis. One-year, randomized, placebo-controlled trial. 83 patients with severe ulcerative colitis were enrolled. Fifty patients who relapsed within two months on corticosteroid withdrawal were randomized into two groups. The azathioprine group received oral sulfasalazine (6-8 g/day), oral prednisolone (1 mg/Kg/day) and oral azathioprine (2 mg/Kg/day). The placebo group received oral sulfasalazine (6-8 g/day), oral prednisolone (1 mg/Kg/day) and placebo. Corticosteroids were tapered over 12-16 weeks. Five patients (2 in azathioprine group, 3 in placebo group) dropped out of the study. Three patients in the azathioprine group had side effects. The number of patients going into complete remission and partial remission was not significantly different in the two groups. The proportion of relapses in the azathioprine group was lower than in the placebo group (p < 0.05). In patients with ulcerative colitis, azathioprine had no effect in achieving remission, when given in combination with prednisolone; however, it lowers the proportion of relapses. Side effects like pancreatitis and hepatitis are mild and respond promptly to drug withdrawal.