Recent studies have shown that cholecystokinin (CCK) is involved in the induction and development of acute pancreatitis in experimental animals. In the present study we determined basal plasma CCK concentrations by a specific and sensitive radioimmunoassay using antiserum OAL656 in 17 patients with acute pancreatitis due to gallstone in the common bile duct (n= 7), alcoholic (n= 4), post endoscopic retrograde pancreatography (n= 1), and unknown causes (n= 4), and 37 patients with cholelithiasis (n= 18) and choledocholithiasis (n= 19). Plasma CCK concentrations in patients with gallstone pancreatitis on hospital day 1 (mean ± SEM, 6.78 ± 1.39 pM) were significantly higher than those in patients with other causes (1.33 ± 0.16 pM) or in 20 healthy control subjects (1.55 ± 0.11 pM). There was no relationship between plasma CCK and serum pancreatic enzyme levels, the severity of acute pancreatitis, or serum bilirubin concentrations. Plasma CCK levels in patients with acute symptomatic cholelithiasis (n= 7; 4.35 ± 0.90 pM) and choledocholithiasis (n= 8; 4.52 ± 1.17 pM) were significantly higher than those in patients without symptoms (cholelithiasis,n= 11, 1.40 ± 0.17 pM; choledocholithiasis,n= 11, 1.88 ± 0.49 pM) but tended to be lower than those in patients with gallstone pancreatitis. These present observations suggest that the increase in plasma CCK levels in gallstone pancreatitis appears not to be the cause but to be the result of gallstone pancreatitis probably due to a transient disturbance of bile flow into the duodenum by stones or edema of the bile duct. Our present results provide some evidence for the usefulness of CCK receptor antagonists for the treatment of biliary colics and acute pancreatitis.