Exocrine and endocrine function of the pancreas was assessed in the early postoperative period (< or = 2 months) and subsequently (mean, 25 months; range, 3 to 120) in 103 patients (69 men, 34 women; mean age, 42.4 +/- 11.6 years) undergoing operation for chronic pancreatitis. Alcohol was the main causative agent (69%) and pain the most frequent indication (87%) for operation. Drainage procedures (n = 23) did not alter pancreatic function either initially or on long-term follow-up. In the early postoperative period, distal pancreatectomy (n = 42) often impaired endocrine function without affecting exocrine function; seven patients (17%) became diabetic, and results of oral glucose tolerance test showed deterioration in 23 of 28 patients (82%, p < 0.05). On subsequent follow-up, 11 patients developed exocrine failure (p < 0.01) and 10 patients endocrine (p < 0.01) failure. Proximal pancreatectomy (n = 38) precipitated clinical exocrine failure in 14 patients (37%, p < 0.01), yet pancreolauryl tests in 18 patients showed little objective change in exocrine status (0.50 > p > 0.10). Endocrine function was initially spared after proximal pancreatectomy, but six additional patients (16%, p < 0.05) required treatment for diabetes at a mean of 19 months (range, 3 to 34). Deterioration in pancreatic function is thus not an invariable immediate consequence of pancreatic drainage procedures or partial pancreatectomy for chronic pancreatitis. Progression of disease must account, in part, for failure of both exocrine and endocrine function on long-term follow-up. Drainage operations appear to delay this progressive decline in pancreatic function.