Plasma concentrations of cholecystokinin (CCK) have been reported to be elevated in patients with chronic pancreatitis. The elevations are suggested to be due to increased release of CCK from the upper small intestine secondary to the absence of protease activity (trypsin and chymotrypsin) in the intestinal lumen. We have studied plasma CCK levels before and after liquid as well as solid meals in eight patients with pancreatic insufficiency due to advanced chronic pancreatitis and in eight healthy controls. CCK concentrations were measured with a sensitive and specific radioimmunoassay using an antibody directed against the sulfated tyrosyl region of CCK. No differences in basal or maximal postprandiel plasma CCK levels between patients and controls were observed. In the liquid meal study, basal CCK concentrations in patients and controls were 2.2 ± 0.7 and 2.5 ± 0.4 pM, respectively, with maximal postprandial concentrations of 9.6 ± 2.2 and 11.2± 1.4 pM. In the solid meal study, basal CCK concentrations in patients and controls were 2.5 ± 0.6 and 2.6 ± 0.4 pM, respectively, with maximal postprandial concentrations of 9.4 ± 1.6 and 8.6 ± 1.4 pM. The only difference observed was a significantly longer time interval to maximal plasma CCK levels in patients as compared with controls after the liquid meal. Two patients with no detectable trypsin activity in the small intestinal lumen during a Lundh test meal had basal CCK levels of 1.3 and 1.8 pM. Thus, the present study does not support the hypothesis that trypsin is involved in the regulation of CCK release. It is concluded that both basal and postprandial plasma CCK concentrations are normal in patients with pancreatitis insufficiency due to advanced chronic pancreatitis.