Dissolution of bile duct calculi is complicated by the facts that about 30-40% of them are pigment stones and the stone cannot be unambiguously identified by radiography before the start of therapy. Thus it does not appear logical only to infuse irrigation media that dissolve cholesterol (cholate, Capmul) but to use solutions that also dissolve calcium bilirubinate. Calcium bilirubinate is the most important compound in primary pigment stones in the bile duct. Thin sections of calcium bilirubinate stones can be dissolved in EDTA 4Na. The rate is determined by the temperature, the pH, and the surface tension of the solution. In vitro experiments showed that cholesterol stones and composition stones can be dissolved more rapidly by alternating therapy with an EDTA solution and a Capmul preparation than by monotherapy with glycerol octanoate, and that bovine pigment stones can also be disaggregated. Since calcium bilirubinate stones consist up to 20-60% of an organic matrix, a mixture of glycerol octanoate and EDTA was prepared containing SH-activated papain. It was possible, by using this mixture, to disaggregate human calcium bilirubinate stones. The process of dissolution is complex and is not yet understood in detail. It is supposed that the important steps are the extraction of calcium, the chemical solution and molecular dispersion of bilirubin and cholesterol, and the disaggregation of the structure of the stone by surface-active substances. The irrigation media have but little effect on black pigment stones. Toxicity studies have shown that cholate, glycerol octanoate, and glycerol octanoate preparations are locally toxic and can lead to cholangitis and cholecystitis in animals. EDTA solutions bring about lesser changes. In humans, it has not been possible to distinguish these inflammatory changes unambiguously from those found in untreated gallstone patients.