The long-term treatment of metastasizing medullary thyroid carcinoma with octreotide was evaluated in seven patients with progressive disease. All patients had persistently elevated serum calcitonin and carcinoembryonic antigen (CEA) concentrations. Daily doses of 200-1000 micrograms octreotide were administered by means of two or three subcutaneous injections for 3-9 months. In one patient treatment was stopped after 3 days because of aggravation of preexisting diarrhea. No beneficial effect on preexisting diarrhea was observed in three other patients during long-term treatment; in these patients further weight loss occurred. In five of six patients, serum calcitonin concentrations further increased; serum CEA concentrations increased in four of six patients. A therapeutic effect on tumor growth could not be demonstrated; in three patients, metastases continued to grow. We conclude that octreotide does not improve the natural course of advanced stages of medullary thyroid carcinoma.