The hypolipidemic effects of fluvastatin sodium (XU 62-320, CAS 93957-55-2), a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, were examined. Fluvastatin sodium was administered to Watanabe heritable hyperlipidemic (WHHL) rabbits, a low density lipoprotein (LDL) receptor deficient animal model, for 6 weeks at doses of 12.5 mg/kg, 25 mg/kg, and 50 mg/kg. Total cholesterol levels in serum, in very low density lipoproteins (VLDL), in intermediate density lipoprotein, and in LDL decreased dose-dependently. In the 50 mg/kg group, cholesterol reduction in each of the aforementioned segments was 50%, 91%, 94% and 33%, respectively. The secretion rate of VLDL-cholesterol, as determined by intravenous injection of Triton WR-1339, also decreased in a dose-dependent manner, showing a reduction of 16% (p < 0.05) in the 50 mg/kg group. In addition, the cholesterol content of newly-secreted VLDL also decreased dose-dependently. These results indicate that fluvastatin sodium has a potent hypolipidemic effect, and suggest that one of the mechanisms responsible for the reduction of serum cholesterol may be the suppression of VLDL-cholesterol secretion.