Five patients with Zollinger-Ellison syndrome (ZES) have been treated during 9-12 months with long-acting somatostatin (SMS 201-995). Basal acid output presented a sustained decrease in 4 of 5 cases, below 10 mmol/h in three patients, allowing ranitidine discontinuation. No escape phenomenon was observed. Maximal acid secretion progressively decreased, suggesting an SMS antitrophic effect. Serum gastrin level was affected in a greater extent, showing a mean 87% decrease throughout the treatment period. Thus three patients kept normal serum gastrin levels in the long-term; one escaped to SMS after 9 months. Associated endocrine neoplasia were poorly influenced by SMS. No convincing evidence of tumor size variation was noted. Tolerance of SMS was excellent in the five patients. SMS' antitrophic and antigastrin properties could be of great interest in long-term management of ZES.