Five pancreatic cutaneous fistulas were treated by subcutaneous administration of a long-acting synthetic analog of somatostatin, SMS 201-995. Patients included four men and one woman who ranged in age from 52 to 77 years. The fistulas developed after drainage of a pancreatic abscess, biopsy of a pancreatic mass, splenectomies for idiopathic thrombocytopenic purpura and Felty's syndrome, and operative trauma, respectively. Fistula output consisted of 1,000 ml/day of amylase- and lipase-rich fluid in the patient with a pancreatic biopsy. The other four patients had low-output fistulas (100 to 250 ml/day) that had been draining for 1 to 12 months. Direct communication with the pancreatic duct was demonstrated by endoscopic retrograde cholangiopancreatography, sinography, or both in four of the five patients. Fistula output decreased from 340 +/- 376 ml/day to 63 +/- 36 ml/day on the first day of therapy with two daily doses of 0.05 mg SMS 201-995 (p less than 0.03) and to 13 +/- 19 ml/day on the seventh day of therapy (p less than 0.03). Two patients had prompt closure of their fistulas and one closed in 3 months. One patient with chronic pancreatitis and a duct stricture and one patient with recurring infection did not achieve permanent fistula closure with SMS 201-995. Because of its safety, ease of administration, and efficacy in decreasing fistula output, we believe somatostatin analog therapy is beneficial in hastening closure of pancreatic fistulas.