An association exists between cigarette smoking and pancreatitis owing to alcohol. We determined whether cigarette smoking affected the course of pancreatic calcification and insufficiency in idiopathic chronic pancreatitis. Medical records were analyzed of 24 persons with early- and 42 with late-onset idiopathic chronic pancreatitis who were diagnosed between 1976 and 1982 and then followed prospectively until 1985. Smoking equaled >5 pack-years before calcification or insufficiency or last follow-up. Mean follow-up after onset of chronic pancreatitis was 27 and 13 years in early- and late-onset idiopathic chronic pancreatitis, respectively. Incidence of calcification in the two groups was 58 and 43%, respectively. In early-onset idiopathic chronic pancreatitis, smokers and nonsmokers developed calcification at a similar rate and frequency (58%). In late-onset idiopathic chronic pancreatitis, smokers developed pancreatic calcifications faster (p < 0.001) and more frequently (83 vs. 13%, p < 0.001) than nonsmokers. The association between smoking and pancreatic calcification was independent of gender, body mass index, and exocrine or endocrine insufficiency. Smoking did not affect development of exocrine or endocrine insufficiency. Cigarette smoking increases the risk of pancreatic calcification of late- but not of early-onset idiopathic chronic pancreatitis. These data support encouraging cessation of smoking in chronic pancreatitis.