Antral gastrin and somatostatin mRNA concentrations were measured in rats during gastric neutralization produced either by resection of the acid-secreting portion of the stomach (fundectomy) or by omeprazole treatment. Fundectomy caused increases in gastrin mRNA concentrations to 570% of sham control after 4 days and to 650% after 28 days. Daily administration of omeprazole resulted in significant dose- and time-dependent increases in antral gastrin mRNA concentrations. Four-day treatment with omeprazole caused threefold increased gastrin mRNA. Antral somatostatin mRNA concentrations decreased significantly after fundectomy to 66% of sham control after 4 days and to 23% after 28 days. Omeprazole produced a more profound decrease in somatostatin mRNA to 22% of the vehicle control after 4 days. Antral beta-actin mRNA concentrations did not differ significantly between control and experimental animals. Transcription of gastrin mRNA in isolated antral mucosal nuclei, measured by a nuclear run on technique, was significantly increased after omeprazole treatment in vivo. Increases in plasma and antral gastrin concentrations in response to gastric neutralization were closely associated with increases in gastrin mRNA and were accompanied by reductions in somatostatin mRNA in the antrum. However, fundectomy produced relatively greater increases in gastrin mRNA and lesser reductions in somatostatin mRNA than observed after omeprazole pretreatment.