INTRODUCTION : Mesenteric ganglia & abundant nerve bundles in the sphincter musculature generate evoked potential by the activity of galanin containing neurones & catecholamine containing neurones. NANC, CGRP, VIP, Peptide YY, NO & Somatostatin regulate sphincter mechanism. METHODS : Histopathology of 30 specimens of Sphincter of Oddi (SO) from cadavers of both sexes & of different ages with no history of pancreaticobiliary diseases were studied. SOD Manometery, ERCP & scintigraphy on 125 patients with biliopancreatic disease - cholelithiasis (70), acute pancreatitis (30) post cholecystectomy syndrome (25) were analysed. RESULTS : There were two functional segments of the Sphincter of Oddi arranged into C1 to C5 groups of fibres. Alteration of the mucous glands in the form of Adenomatosis (75%), Centrifugal proliferation of glands (75%), club like valvulae (50%), obstruction in neck of glands (50%), increased goblet cells (75%), adeno connective dysplasia (50 %), inflammatory infiltration (100%), muscular hypertrophy (±), sclerosis ( ± ). SO Dysfunction : Abnormality on SOD manometery (45%), scintigraphy (17%), ERCP (38%); in the form of rhythmic contractions 4-5 / min, antegrade, duodenum, retrograde, gallbladder ; integrated with MMC of duod, with 5-15 mm Hg of CBD, & 15 - 30 mm Hg pressure of duod. Gradient - CBD/Duodenum : 15 mm Hg, PD/ Duodenum : 17 mm Hg; Basal SO - 15 ± 10 mm Hg; Phasic SO - Amplitute 130 ± 16 mm Hg, Frequency 4 ± 0.5 p/min, Duration 4.3 ± 1.5 sec. Abnormal biliary motility includes : Basal sphincter pressure > 15 mm Hg, Basal PHD / CBD pressure > 13 mm Hg, Phasic amplitudes > 220 mm Hg, Duration of phasic contractions > 8 sec &, Propagation > 50 % retrograde & increased amplitude of phasic contraction, increased frequency of contraction & paradoxical response to CCK. Sphincter dyskinesia was rapid phasic contractions, intermittent increased basal pressure, increased retrograde contractions & paradoxical response to CCK by sphincter contractions instead of relaxation. SOD dysfunction was classified on Milwaukee criteria & treated by endoscopic sphinctertomy, pharmacotherapy & Botulinum toxin inadditon to the treatment of biliopancreatic disease. CONCLUSION : The histological alterations in SO indicate reactive changes to repeated physical, chemical & inflammatory insult. SOD manometery, scintigraphy & ERCP reveal SO dysfunction in bilio-pancreatic diseases with specificity of 78%, positive predictive value of 83%. Endoscopic or open sphinctertomy were effective in treating SOD.