Our preliminary studies showed that in mildly hypercholesterolemic rats with chemically induced breast cancer, dietary orange juice reduced total plasma cholesterol and dietary grapefruit juice tended to reduce VLDL + LDL cholesterol. We therefore investigated whether orange juice and grapefruit juice (double strength) could influence cholesterol metabolism in rabbits with high LDL cholesterol levels induced by feeding a semipurified, cholesterol-free, casein diet. In animals fed the experimental diet for 3 weeks, replacing drinking water with either:orange juice or grapefruit juice reduced serum LDL cholesterol by 43% and 32%, respectively (p < 0.05). This was associated with total liver cholesterol reduction in the orange juice group (-18%, p < 0.05) and with hepatic cholesterol ester reduction in both juice groups (-42%, p < 0.05). The juices were not acting as intestinal sequestrants since neither increased fecal cholesterol or bile acid excretion. In fact, cholesterol excretion was-decreased in both orange juice and grapefruit juice group by 44% and 48%, respectively (p < 0.05). These results suggest that the reduction of LDL cholesterol induced by dietary citrus juices could be due to endogenous effects of juice components, possibly flavonoids. (C) 1999 Elsevier Science Inc.