Aim. To comprehensively study of the function of digestive organs in cholelithiasis (CL). Subjects and methods. Three hundred and seventeen patients with the early (prestone) stage of CL were examined. The latter was verified by ultrasonography (USG) and biochemical bile tests. The patients underwent pH metry and esophagogastroduodenoscopy, followed by histological examination of gastroduodenal mucosa (GDM) biopsy specimens. Manometry was used to evaluate duodenal function. The serum levels of pepsinogen-1 (PG-1), pepsinogen-2 (PG-2), cholecystokinin (CCK), gastrin, cyclic nucleotides (cAMP and cGMP), α1-antitrypsin, insulin, and C-peptide were analyzed by an enzyme immunoassay. Small intestinal function was examined using a set of diagnostic tests. Results. Gallbladder USG revealed biliary sludge in 273 (86.1%) patients. Biochemical examination of bile established a lower cholatocholesterol coefficient in its cystic as well as hepatic portions, suggesting enhanced bile lithogenicity. Manometry of the duodenum showed its hypertension, hypotension, and normotension in 57.6, 24.8, and 17.6% of the CL patients, respectively. There were significant increases in basal gastric body pH and PG-1 and PG-2 levels as compared to the control group. Morphological examination of GDM biopsy specimens revealed chronic superficial gastritis in 61.8% of the patients, chronic atrophic gastritis in 17.4%, and moderate diffuse duodenitis in 18.3%. In 148 (46.7%) patients with CL, the latter was burdened by pancreatic comorbidity. Stress tests using water-soluble starch, sucrose, and glucose demonstrated impairments in various stages of digestion; substantially decreased levels of CCK, gastrin and cyclic nucleotides were observed in the patients with CL compared to the controls. Conclusion. Most patients with CL were detected to have digestive organ structural and functional disorders. Moreover, CL may be regarded as a possible manifestation of systemic digestive diseases.