BACKGROUND: The correlation between disease activity and endoscopic findings in Crohn's disease is poor. Corticosteroids induce symptom relief without consistent improvement of endoscopic lesions. Our aim was to examine the effect of azathioprine therapy on healing of inflammatory lesions in patients with severe Crohn's disease. METHODS: The study included 20 consecutive patients with Crohn's colitis or ileocolitis in clinical remission while taking azathioprine for at least 9 months and no corticosteroids for at least 3 months who had had an ileocolonoscopy less than 1 year before the start of azathioprine. All 20 patients underwent a new ileocolonoscopy with biopsies. RESULTS: The duration of azathioprine therapy was 24.4 +/- 13.7 months. In the colon, we observed complete healing in 14 of 20 patients (70%), near-complete healing in 2 of 20 (10%), partial healing in 3 of 20 (15%), and no healing in 1 of 20 (5%). In the ileum complete healing was seen in 7 of 13 (54%) patients with ileitis, near-complete healing in 2 of 13 (15%), partial healing in 1 of 13 (8%), and no healing in 2 of 13 (15%); the ileum was not reached in 1 patient. Histologic examination revealed disappearance of the inflammatory infiltrate, with a certain degree of architectural disturbance remaining. CONCLUSIONS: Successful azathioprine therapy is accompanied by mucosal healing and disappearance of the inflammatory infiltrate.