Long-chain triglycerides inhibit gastric acid secretion, but the effect of medium-chain triglycerides in humans is unknown. We compared the effects of intraduodenally perfused saline, medium-chain and long-chain triglycerides on gastrin-stimulated gastric acid secretion and cholecystokinin release. Eight healthy male volunteers participated in this study. Gastrin-stimulated gastric acid output was 9.4 +/- 1.1 mmol/30 min during saline perfusion. It was suppressed by medium-chain triglycerides by 43 +/- 9% (P = 0.04 vs. saline) and by long-chain triglycerides by 74 +/- 6% (P = 0.0003 vs. saline). Thus medium-chain triglycerides inhibited gastrin-stimulated gastric acid secretion but less so than long-chain triglycerides. When compared to saline perfusion (73 +/- 6 pM x 30 min) integrated plasma cholecystokinin concentrations were significantly elevated by long-chain triglycerides (96 +/- 5 pM x 30 min, P < 0.004) but not by medium-chain triglycerides perfusion (65 +/- 7 pM x 30 min). We also investigated the role of cholecystokinin infusion on gastrin stimulated gastric acid secretion. Higher concentrations (191.4 +/- 4.5 pM x 30 min) of CCK than released in the long-chain triglycerides perfusion experiment, did not suppress gastric acid secretion. Thus, circulating cholecystokinin appears not responsible for the inhibition of gastrin-stimulated gastric acid secretion by dietary fat.