BACKGROUND Gastric lipase is an important enzyme for dietary triglyceride digestion in normal subjects. Its regulation is unknown, as is the relation between the quantity and activity of the enzyme. METHODS In a dose-response study we investigated the effect of low doses of pentagastrin (less than 1000 ng/kg/h) on the output of gastric lipase measured by a kinetic assay and an enzyme-linked immunosorbent assay (ELISA). RESULTS In five healthy volunteers stepwise intravenous pentagastrin infusions of 0, 50, 100, 500, and 1000 ng/kg/h resulted in a stepwise increase in the lipase output, as measured with ELISA. However, the lipolytic activity, measured with a kinetic assay, decreased as the pH of the gastric contents decreased. CONCLUSIONS We conclude that secretion of the gastric lipase is stimulated by pentagastrin, but the simultaneous secretion of acid counteracts the lipolytic activity of the enzyme when food is not present.