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Abstract Background The pathogenesis of idiopathic pancreatitis (IP) remains poorly understood. Our hypothesis is that IP is a sequel of micro-crystallization of hepatic bile. Methods A prospective case control study compared 55 patients; symptomatic cholelithiasis - 30 (14 male, median age 36 years; mean BMI - 25.1 kg/m2), gallstone pancreatitis - 9 (3 male, median age 35 years; mean BMI - 24.86 kg/m2 ) and IP - 16 (9 male, median age 34 years; mean BMI -23.34 kg/m2) with 30 controls (15 male, median age 38 years; mean BMI = 24.5 kg/m2) undergoing laparotomy for conditions not related to the gall bladder and bile duct. Ultrafiltered bile from the common hepatic duct in patients and controls was incubated in anaerobic conditions and examined by polarized light microscopy to assess bile nucleation time (NT). In the analysis, the mean NT of patients with gallstones and gallstone pancreatitis was taken as a cumulative mean NT for those with established gallstone disease (EGD). Results Patients were similar to controls. Mean NT in all groups of patients was significantly shorter than controls (EGD cumulative mean NT, 1.73 +/- 0.2 days vs. controls, 12.74 +/- 0.4 days, P = 0.001 and IP patients mean NT, 3.1 +/- 0.24 days vs. controls, 12.74 +/- 0.4 days, P = 0.001). However, NT in those with IP was longer compared with those with EGD (mean NT in IP, 3.1 +/- 0.24 days vs. cumulative mean in EGD: 1.73 +/- 0.2 days, P = 0.002). Conclusion Nucleation time of bile in patients with IP is abnormal and is intermediate to nucleation time of lithogenic bile at one end of the spectrum of lithogenicity and non-lithogenic bile, at the other end.