This study reports the effects of 4 and 5-year treatment with octreotide (200 micrograms sc bid) in the Zollinger-Ellison syndrome (ZES). No symptoms related to acid hypersecretion were observed in the four patients throughout the study, and upper GI endoscopy was normal. Basal acid output (BAO) measured 12 h after injection, was below 10 mmol h-1 in three to four patients and previous ranitidine treatment was discontinued. In the fourth case (pretreatment BAO value: 115 mmol h-1), BAO progressively decreased to 42 mmol h-1 after 5 years of octreotide treatment. At the end of the study, serum gastrin levels were 58.5% (30-68) of the pretreatment values and two patients had normal gastrin levels. Peak acid output (PAO) decreased markedly after 2, 4 and 5 years, by 68% (35-89) suggesting that octreotide had exerted an antitrophic effect on parietal cell mass. Diffuse hyperplasia of fundic argyrophil cells present in two patients before octreotide, decreased during the treatment. Mean argyrophil cell density for all patients was not significantly modified. Antral gastrin-cell density was in the normal range. No long-term side effect of octreotide treatment was observed. Although octreotide may not be considered as a substitute for benzimidazoles in the treatment of ZES, its specific properties may be of therapeutic benefit in some ZES patients.