A new possible pathogenesis of gallstones is described. The theory is based on the presence of indolic melanin precursors in biological fluids. It is proposed that the increased concentration of these compounds in bile could lead to the formation of melanin polymer as a network nucleus for a future concrement. An activation of the pigmentary system (e.g. insolation, gravidity) and the presence of hydrolytic enzymes (β-glucuronidase and/or arylsulphatase) in biliary tract might belong to the risk factors of gallstone formation. The detection of 5-hydroxy-6-methoxyindolyl-2-carboxylic acid in bile and 5,6-dihydroxyindole in the extract of an alkali fused gallstone provided the first support of this theory.