Quantitative ultrastructural studies of human gastric mucosal chief cells during secretory stimulation have not been reported previously. In five healthy subjects we studied the effect of intravenous administration of 2 CU/kg of GIH secretin on gastric chief-cell ultrastructure. Gastric biopsies for quantitative ultrastructural analysis were obtained before and 15 and 30 min after secretin administration. Electron micrographs of 150 chief cells were analyzed by the Loud quantitative method. After secretin administration the percentage area occupied by zymogen granules decreased significantly at 15 and 30 min. At corresponding times membrane profile concentration (rough endoplasmic reticulum) increased significantly over basal values. This study provides morphological evidence of increased activity of chief cells after secretin administration.