Chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) dissolve cholesterol gallstones in man. Since CDCA has caused liver damage in animal experiments we have tried to elucidate the question whether such alterations could occur due to UDCA therapy as well. CDCA and UDCA were fed orally in doses of 20, 90, 150, 250 and 1000 mg/kg body-weight daily to female Wistar-Rats (CDCA: 75 animals; UDCA: 75 animals). After 5, 30 and 60 days we examined the liver by means of light- and electronmicroscopy. After 30 days all animals treated with 1000 mg/kg CDCA had died, whereas there were no pathological findings in the UDCA treated group. By means of electronmicroscopy we detected in the CDCA-group already with 20 mg/kg/day microstructural alterations of the liver that increased with elevation of the dosage and duration of treatment. With UDCA therapy liver tissue showed minimal changes only with 1000 mg/kg. The difference is explained by the decreased rate of transformation of UDCA to lithocholic acid and the lack of toxicity of UDCA in the hepatocyte.