Guinea pigs were fed increasing concentrations of citrus pectin (CP) (0-12.5%, wt/wt) with low (LC, 0.04%) or high (HC, 0.25%) cholesterol. Animals fed LC diets had reduced plasma LDL concentrations with 10% and 12.5% CP and hepatic membrane apolipoprotein B/E receptor expression increased with high dosages of CP. Hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity increased with 12.5% CP whereas hepatic cholesterol concentrations and acyl-CoA:cholesterol acyltransferase (ACAT) activity were not different. In contrast, with HC diets, plasma LDL concentrations were reduced in a dose-response manner by 29%, 30%, and 67% with 7.5%, 10%, and 12.5% CP intake (P < 0.001) and apolipoprotein B/E receptor number was increased and inversely correlated with plasma LDL in the HC group (r = -0.81, P < 0.005). Animals fed HC diets had a dose-dependent decrease in hepatic cholesterol and ACAT activity, with intake of 12.5% CP having the major effect. Hepatic HMG-CoA reductase activity was suppressed by HC diets and only intake of 12.5% CP reversed this suppression. The most significant effects of CP on hepatic cholesterol, enzymes of hepatic cholesterol homeostasis, and the apolipoprotein B/E receptor were in animals fed the HC diets. These metabolic alterations partially explain the reduced plasma LDL of guinea pigs fed large amounts of CP.