The chemical dissolution of human brown pigment stones was studied using various monophasic multicomponent solvents. Among the nine solutions tested for stone powder dissolution capacity, the two most active were retained for further analysis. The solvent containing 26 mM ethylenediaminetetraacetate, 40 mM sodium deoxycholate, 10 mM monoolein and 30% dimethylsulfoxide was efficient for calcium and bilirubin solubilization. The other solvent containing dimethylsulfoxide/methyl tert-butyl ether (70:30) had a high capacity for dissolution of cholesterol and bilirubin. From in vitro stone dissolution experiments, we found that alternating treatment every 2 h with these two mixtures was more effective than using these solvents separately. Within 24 h, 90% of cholesterol, 80% of bilirubin, and 70% of calcium were dissolved. In vivo, we studied the dissolution of human stones surgically implanted in the gallbladder of 6 rabbits. Alternating perfusions with the solvents selected led to complete disappearance of stones within 16 h in 5 out of 6 cases. The residual histological toxicity in the gallbladder wall, 15 days after perfusion, was low and blood parameters did not differ from the normal values.