Development of focal gland atrophy of the oxyntic mucosa was found in two patients with the Zollinger-Ellison syndrome undergoing long-term treatment with omeprazole. The atrophic areas revealed florid proliferation of endocrine cells in the form of both intraglandular crescents and micronodular hyperplasia. This proliferation was significantly more pronounced than in the remaining non-atrophic mucosa. The possible relationship of these changes to long-standing pharmacological therapy for gastric acid suppression is discussed.