The effect of infusing isotonic saline, isotonic and hypertonic glucose, fat emulsion, amino acids. ethanol, and hydrochloric acid into the duodenum on the plasma concentration of immunoreactive secretin was studied in seven normal subjects. Only hydrochloric acid showed any effect. After acidification of the duodenum with hydrochloric acid a significant rise in plasma secretin concentration was observed from 1.3 +/- 0.4 pmol X 1(-1) (mean +/- SEM) to a peak value of 13.0 +/- 1.2 pmol X 1(-1) after 5 min. The concentration returned to the basal level within 15 min. In eight other normal subjects the plasma secretin concentration was measured after the ingestion of a protein-rich meal. No significant changes were observed during the 2 h postprandial period.