Cholecystokinin (CCK) response to a test meal should be increased in patients with pancreatic insufficiency, as trypsin is absent from the duodenum. If pancreatic enzymes are added, a restoration of the inhibitory feedback should result in lower levels of CCK. Ten patients with chronic pancreatitis and steatorrhea were studied. CCK basal and postprandial levels were evaluated the day before and 45 and 90 days after treatment with oral pancreatin. Twelve healthy volunteers were included as reference group. CCK basal levels did not vary. CCK response to a test meal was increased in patients before treatment and diminished when oral enzymes were maintained for months even after three days of therapy withdrawal. We conclude that long-term therapy with oral enzymes induces changes in CCK response that do not regress after three days of treatment suspension.