In rats, hypergastrinemia due to achlorhydria produced by antisecretory drugs or resection of the gastric fundus leads to enterochromaffinlike (ECL) cell hyperplasia and gastric carcinoids. In humans, achlorhydria due to pernicious anemia may also lead to ECL cell hyperplasia and multicentric gastric carcinoids in as many as 5% of cases. To examine the apparent gastrin dependence of gastric ECL carcinoids, three patients were studied (2 men aged 59 and 73 years; 1 woman aged 45 years) who had pernicious anemia, serum gastrin concentrations of greater than 1000 ng/L (greater than 1000 pg/mL), and multicentric gastric carcinoids. Antrectomy resulted in normalization of serum gastrin levels within 8 hours and disappearance of carcinoids in 6-16 weeks. In each of the three patients, a focus of microcarcinoid was found at 12-18 months. Further follow-up in each of the three patients 21-30 months after antrectomy again showed no carcinoids or ECL cell hyperplasia. It is concluded that multicentric ECL gastric carcinoids in patients with pernicious anemia and achlorhydria appear to be gastrin dependent and disappear after normalization of serum gastrin by antrectomy. Antrectomy rather than total gastrectomy may be the most appropriate treatment for this condition.