A double-blind therapeutic trial of azathioprine in 20 patients with acute proctocolitis was performed over a 3-month period. Azathioprine was compared with sulfasalazine in patients paired and treated in a sequential order. Clinical, laboratory, endoscopic, biopsy, and radiologic data were assessed by semiquantitative criteria. No significant difference in the effect of the drugs was observed. Both azathioprine and sulfasalazine produce significant improvement in clinical symptoms, some laboratory findings (ESR, serum iron), and endoscopic and biopsy findings (P smaller than 0.05). Radiologic improvement was less evident (P smaller than 0.10). On the overall final evaluation of the trial, 14 patients were improved, and 6 remained stationary or worsened (P smaller than 0.10). This short-term trial confirms previous uncontrolled experiences of one of the authors on larger series of patients.