The treatment of malignant neuroendocrine gut and pancreatic tumors provides a therapeutic challenge. Surgery as well as medical treatment rarely cure the patient at this stage. Symptoms related to secretory products from the tumor might be life-threatening or at least reduce the quality of life considerably. Interferons (IFNs) have demonstrated an antitumor effect in multiple tumor diseases and were introduced by our group in 1982 for the treatment of carcinoids. Today, more than 300 patients with various neuroendocrine tumors and who receive alpha-IFN have been reported in the literature. Treatment of midgut carcinoid tumors at doses of 3-9 MU 3-7 times per week subcutaneously has achieved biochemical responses in 44% of the patients with significant tumor reduction in 11%. Subjective improvement has been obtained in around 65% of the patients. A median survival from start of treatment in patients with carcinoid syndrome of 80+ months has to be compared with 8-12 months on chemotherapy (streptozotocin plus 5-FU). Treatment of endocrine pancreatic tumors with alpha-IFN at doses of 5-6 MU 3-5 times per week achieved biochemical responses in 51% of the patients and tumor responses in 12%. The median duration of response was 20 months (range 2-96). Combining alpha-IFN with the somatostatin analogue octreotide in patients with malignant tumors resistant to octreotide alone got biochemical responses in 77% with 18% complete biochemical remissions. No significant reduction of tumor size was noticed, but stabilization of the disease was obtained for a median of 15 months.(ABSTRACT TRUNCATED AT 250 WORDS)