Pancreatic ductal stones may be responsible for attacks of acute pancreatitis (chronic relapsing pancreatitis) or exacerbations of chronic pain in patients with chronic pancreatitis. This study was undertaken to identify those patients with predominantly main pancreatic duct stones most amenable to endoscopic removal and to determine the effects on the patients' clinical course with such removal. Thirty-two patients with ductographic evidence of chronic pancreatitis and pancreatic duct stones underwent attempted endoscopic removal. Of the patients, 71.9% had complete or partial stone removal and 67.7% improved after endoscopic therapy. Symptomatic improvement was most evident in the group of patients with chronic relapsing pancreatitis. Factors favoring stone removal included (1) three or less stones, (2) stones confined to the head and/or body of the pancreas, (3) absence of a downstream stricture, (4) stone diameter less than or equal to 10 mm, and (5) absence of impacted stones. After successful stone removal, 25% of patients had regression of the ductographic changes of chronic pancreatitis and 41.7% had a decrease in the main pancreatic duct diameter. The only complication from therapy was mild pancreatitis in 8.2%. These data suggest that removal of pancreatic duct stones may result in symptomatic improvement. A longer follow-up will be necessary to determine whether endoscopic success results in long-standing clinical improvement and/or permanent regression of the morphologic changes of chronic pancreatitis.