OBJECTIVE: Steroid treatment failure in acute Crohn's disease and ulcerative colitis frequently necessitates surgical intervention. Several alternative therapeutic strategies have been raised. The most promising so far has been intravenous cyclosporine, but the results in the long term have been discouraging. We assessed the efficacy and safety of the new macrolide immunomodulator tacrolimus as an alternative to cyclosporine A. METHODS: Eleven patients with steroid-refractory disease (six ulcerative colitis, two indeterminate colitis, two Crohn's disease, one pouchitis) and severe activity according to the Truelove and Witts criteria or Crohn's disease activity index > 150, respectively, were eligible for the study. All patients were treated with intravenous tacrolimus for 7-10 days followed by oral treatment over a median period of 7 months (range 0.25-16). Azathioprine and mesalamine were given concomitantly. Steroids were tapered according to clinical activity. RESULTS: Seven of 11 patients achieved remission rapidly, whereas a modest improvement was noted in two. Only two patients required an early and one a delayed colectomy. Moreover, a rectovaginal fistula closure in a case of Crohn's disease and an improvement of pouchitis was observed. A tapering to low dose steroids was possible during oral tacrolimus therapy in all nine responders and remission was maintained in five of them (mean follow-up 9.2 months). The drug was well tolerated and side effects were managed conservatively. CONCLUSION: Tacrolimus induced rapid remission in steroid resistant inflammatory bowel disease in the majority of cases. It appears to be an effective treatment modality that may be superior to cyclosporine with respect to maintenance of remission.