We compared five graded doses of decaffeinated coffee and a widely used protein test meal (Bacto-peptone) as stimulants of acid secretion (intragastric titration) and gastrin release (radioimmunoassay) in eight healthy men. In each subject, for both acid and gastrin, the sums of the responses to all five doses were greater to decaffeinated coffee than to peptone. The mean±SE peak acid output in millimoles per hour was 18.5±2.9 to decaffeinated coffee and 14.7±2.7 to peptone, representing 70% and 55%, respectively, of the peak acid output to pentagastrin. The mean±SEM peak increment over basal rate in serum gastrin in picograms per milliliter was 84.8±4.4 to decaffeinated coffee and 44.8±2.1 to peptone. At equal concentrations, decaffeinated coffee was a more potent stimulant of acid secretion and of gastrin release than peptone. The ingredient(s) of decaffeinated coffee that accounts for its high potency in stimulating acid secretion and gastrin release has not been identified.