Fasting and postprandial serum gastrin concentrations were measured by radioimmunoassay in 9 nonulcer control subjects, 8 subjects with active duodenal ulcer disease, and in 25 subjects who had undergone operations for peptic ulcer disease. The operated patients included 8 with vagotomy, partial gastrectomy, and gastroduodenal anastomosis (Billroth I); 8 with vagotomy, partial gastrectomy, and gastrojejunal anastomosis (Billroth II); and 9 with vagotomy and pyloroplasty. Billroth I subjects had fasting and postprandial serum gastrin concentrations similar to those found in nonulcer and un operated duodenal ulcer subjects. In contrast, Billroth II subjects had basal and postprandial values significantly lower than in any other group tested. Patients with vagotomy and pyloroplasty had significantly higher basal and postprandial gastrin concentrations than any other group. These studies indicate that food entering the duodenum is capable of stimulating gastrin release after the gastric antrum has been resected. Food passing from the stomach directly into the jejunum, after similar gastric resection, results in minimal stimulation of gastrin release. The decrease in gastric acidity which results from vagotomy is not due to decreased gastrin release. Instead, vagotomy in man increases basal and postprandial serum gastrin concentrations.