The occurrence of cholesterol malabsorption and its role in the regulation of cholesterol metabolism were studied in 30 patients with an earlier gut resection and 9 patients with a jejunoileal bypass for treatment of obesity. Fractional cholesterol absorption varied from 0.1% to 70%, and was lowest in jejunoileal bypass (8.3%) associated with severe fat and moderate bile acid malabsorptions and in 15 patients with a long small-intestinal resection (20.4%) associated with severe bile acid and moderate fat malabsorption. Seven resected patients with normal fecal fat and bile acids and 8 resected patients with malabsorption of only bile acid had normal cholesterol absorption. Low fractional cholesterol absorption was associated with a short length of the remaining proximal small intestine, high dietary intake of plant sterol, and high fecal fat and neutral sterol excretions, but not with bile acid malabsorption. In the whole study population, plasma levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol were positively correlated with fractional cholesterol absorption and the amount of total, dietary, and biliary absorbed cholesterol and were negatively correlated with fecal cholesterol elimination as neutral sterols (less so as bile acids) and cholesterol synthesis. The results emphasize that, in patients with ileal exclusion, plasma levels of low-density lipoprotein and high-density lipoprotein cholesterol are regulated more effectively by cholesterol than by bile acid malabsorption. Moreover, although the fecal loss of bile acids is the main determinant in cholesterol elimination and stimulation of cholesterol synthesis in patients with intestinal exclusions, intestinal cholesterol absorption also contributes noticeably to the regulation of cholesterol synthesis.