PURPOSE AND METHODS: Twenty-four patients with rapidly progressive neuroendocrine tumors were treated with a new regimen of continuous infusion fluorouracil for 20 weeks (200 mg/m2/d) together with interferon alfa-2b (5 MU three times per week). Maintenance interferon alfa at the same dose was continued after the initial 20-week period. RESULTS: Of 15 patients with carcinoid tumors, seven (47%) had an objective response, with a median duration of 20.5 months (range, 8.5 to 41), and five (33%) had stabilization of disease for between 3.5 and 42 months. Improvement in symptoms was reported by 10 patients (67%). Three early deaths occurred, all in patients with advanced disease. Of nine patients with neuroendocrine tumors other than carcinoid, three (33%) had an objective response that lasted 2.5 to 24.5 months, and five had disease stabilization for between 2.5 and 16 months. CONCLUSION: These data, particularly in respect to carcinoid tumors, are encouraging, especially since serious complications from treatment were limited. This regimen is not generally toxic, is well tolerated, and offers useful palliation and symptom control in patients with disease that does not respond to simple pharmacologic manipulations.