Metabolic reactions to the increased intake of cholesterol (CH)were studied in ten tupaias (Tupaia belangeri Baf:BIAS, tree shrews), fed a lithogenic diet containing 20% fat and 2% CH. The feeding period was 4 months. Twelve animals on standard diet served as controls.The CH content was determined in serum, bile, liver, heart, skin, kidney, muscle, jejunum, ileum, and in the total body. In vitro synthesis rates of CH were measured in the liver and in different parts of the gut.In animals fed the lithogenic diet, serum CH values exceeded those of controls by a factor of 2. However, of all organs examined only the liver showed a rise in the CH content. In hepatic bile, CH values were 14 times higher than in the controls.Intrahepatic synthesis of CH was suppressed to 7% of the rate in animals on standard diet. In the jejunum, CH synthesis rates were 44%, and in the ileum 15% of those determined in controls.It is concluded that the administration of a high CH diet induces a feedback mechanism which lowers the production of CH in the liver and small intestine. However, this adaptation does not prevent the rise of CH in serum, liver, and bile which finally results in the formation of gallstones in the gallbladder.Chenodeoxycholic acid (CDCA), added to the lithogenic diet in a daily dose of 20mg/kg body weight (BW) in five animals, produced an additional significant increase in the hepatic CH content compared to the animals fed the lithogenic diet without CDCA. Other parameters did not differ between the two groups fed the lithogenic diet with and without CDCA.