Twenty asymptomatic paid volunteers (13 females, 7 males, mean age 34 years, range 21-52 years), underwent endoscopic ultrasonography (EUS) to assess variation in the appearance of ductular and parenchymal features of the pancreas. Following this investigation, 69 patients with chronic abdominal pain of suspected pancreaticobiliary origin were evaluated with EUS followed by endoscopic retrograde cholangiopancreatography (ERCP) and in 16 patients secretin stimulated intraductal pure pancreatic juice (PPJ) collection. Thirty patients were found to have chronic pancreatitis based on clinical, ERCP and/or PPJ data, and EUS was abnormal in 24 of these individuals. All of the 19 patients with abnormal pancreatograms also had an abnormal EUS. Twenty-two of the 30 patients with chronic pancreatitis had early disease (no or minimal changes on ERCP). In this subgroup of patients, the sensitivity of EUS was 86% versus 50% for ERCP (p = 0.01). For all patients, the sensitivity, specificity and accuracy of EUS in diagnosing chronic pancreatitis was 80%, 86% and 84% respectively. Using logistic regression analysis eight EUS features were found to be indicative of chronic pancreatitis including echogenic foci within the gland, focal regions of reduced echogenicity within the gland, increased thickness/echogenicity of the main pancreatic duct (MPD) wall, accentuation of the gland's lobular pattern, cysts, an irregular contour or dilation of the MPD and side branch dilation (p < or = 0.05). Generation of a receiver operating characteristic curve to assess the sensitivity and specificity of EUS in diagnosing chronic pancreatitis based on the number of abnormal findings demonstrated that sensitivity and specificity were optimal when three or more abnormal parenchymal and/or ductular features were found. These results suggest that EUS can play an adjunctive role to ERCP and PPJ in the diagnosis of early chronic pancreatitis.