Aims: In chronic calcific pancreatitis of the tropics, etiology and relationship to developing diabetes mellitus are unknown. Some consider these cases a straightforward secondary type of diabetes, while others suggest selective beta-cell impairment. Testing pancreatic function, we investigated whether selective beta-cell impairment triggers diabetes associated with tropical pancreatitis. Methods: At a Bangladeshi research institute, 8 chronic tropical pancreatitis and no diabetes mellitus subjects, 14 fibrocalculous pancreatic diabetics and 27 matched healthy controls underwent arginine ( endocrine pancreatic function) and secretin ( exocrine pancreatic function assessment) stimulation tests. Results: All patients with clinically-diagnosed, chronic pancreatitis demonstrated pronounced exocrine pancreatic dysfunction with beta-cell functioning differing significantly between the two groups. Compared to controls, patients having tropical pancreatitis and no diabetes showed normal plasma C-peptide values at baseline and after arginine stimulation, while fibrocalculous pancreatic diabetics demonstrated a typical diabetic pattern for plasma C-peptide levels. In contrast, pancreatic beta-cell functioning ( glucagon response to arginine) was preserved in both pancreatitis groups. Conclusion: A preserved pancreatic alpha-cell function in diabetics with advanced chronic pancreatitis of the tropics supports the concept of two different pathogenic mechanisms, one eliciting chronic pancreatitis and the other selective pancreatic beta-cell impairment and subsequent diabetes mellitus. Copyright (C) 2004 S. Karger AG, Basel and IAP.