To evaluate the potential for the chemical dissolution of gallstones, 480 stones from 214 patients were studied. The stones were obtained via surgery or endoscopically. They were classified into cholesterol-rich mixed stones, brown pigment stones and black stones. The composition of bilirubin and cholesterol was determined by Fourier transformed infrared spectroscopy. Two per cent tetrasodium ethylenediamine acetate (EDTA), dimethylsulfoxide (DMSO) or methyl-tert-butyl-ethylene (MTBE) were used to dissolve the stones. To enhance solubility, surfactant polysorbate-20 was used to mix two of the individual three solvents. Methyl-tert-butyl-ethylene was found to have the best dissolution ability (by dry weight) 94, 13.4 and 20% for mixed, brown and black stones, respectively. Dimethylsulfoxide resulted in 13, 14 and 25% dissolution and EDTA 9.5, 13 and 16.5%. In contrast, pure water dissolved 4, 6 and 10.4% of the stones, respectively. A combination of the dissolution agents did not enhance the dissolution rate. In fact, the combination of solvents unexpectedly reduced the solubility of the stones: EDTA/MTBE was 17.5, 6.7 and 16.0%; DMSO/MTBE 43.2, 21.9 and 18.0%; DMSO/EDTA 9.1, 7.0 and 9.6%. In conclusion, cholesterol-rich mixed stones were able to be dissolved using MTBE but results of contact dissolution for gallstones are still far from satisfactory.