BACKGROUND: Monoclonal antibodies to the pro-inflammatory cytokine tumour necrosis factor-alpha have shown efficacy in treating Crohn's disease, but can be immunogenic. Soluble tumour necrosis factor-binding proteins are being studied as potential alternative anti-tumour necrosis factor agents in Crohn's disease. AIM: To investigate the safety and efficacy of onercept, a recombinant form of the natural human soluble p55 tumour necrosis factor receptor, in the treatment of patients with active Crohn's disease. METHODS: In a pilot study, 12 patients with active Crohn's disease were randomized to receive onercept at either 11.7 or 50 mg three times weekly for 2 weeks. Patients were followed up for 6 months after the end of treatment. RESULTS: The Crohn's disease activity index decreased rapidly during treatment in both groups. Seven responses (Crohn's disease activity index decrease of 100 points) were observed over the first 6 weeks of the study, including five remissions (Crohn's disease activity index decrease of 150 points). Improvement was sustained for 2-4 months after stopping treatment. Treatment was well tolerated. No patients developed antibodies to onercept. CONCLUSIONS: Neutralizing the activity of tumour necrosis factor-alpha with its soluble p55 receptor may be valuable in the treatment of patients with Crohn's disease. Larger placebo-controlled trials are indicated.