Twenty sets of three gallstones matched for weight and appearance were selected from 20 surgically resected human gallbladders to test the effect of intracorporeal mechanical fragmentation on gallstone dissolution with methyl tert-butyl ether in vitro. One stone from each set was fragmented by a mechanical lithotriptor and then treated with methyl tert-butyl ether, and one was used as control and was treated intact. The third stone was analyzed for its density pattern on CT and biochemically for its cholesterol and calcium content. On the basis of CT appearance, the stones were classified as noncalcified, partially calcified, or heavily calcified. Mechanical fragmentation reduced dissolution time by 25-69% (mean +/- SD, 44 +/- 16%) for the noncalcified stones and by 20-42% (mean +/- SD, 30 +/- 8%) for the partially calcified stones. No significant reduction was observed for the heavily calcified stones. The degree of reduction was inversely related to maximal stone density (r = -.72) and was independent of its pattern of calcification. This study shows that mechanical fragmentation is effective in accelerating gallstone chemolysis by methyl tert-butyl ether for noncalcified and partially calcified but not for heavily calcified stones.