Background The rate and degree of LDL cholesterol reduction, in the first 2 weeks of therapy, may relate to the early benefit of hydroxymethyl glutaryl coenzyme A reductase inhibitor therapy. In patients with similar baseline LDL cholesterol levels as in the Cholesterol and Recurrent Events (CARE) trial, we report the results of a 2-week placebo-controlled, double-blind investigation of 10 mg/day atorvastatin. Methods and Results The 22 participants were non-Hispanic whites younger than age 72 (average age 47 years) who were modestly overweight and had normal blood pressure. There were no significant baseline lipid and lipoprotein differences. By day 5, there were significant (P <.01) reductions in total cholesterol and LDL levels. The total cholesterol level fell by 25% (226 mg/dL to 169 mg/dL) and LDL cholesterol fell 35% by day 14 (P <.001). Triglyceride levels declined by 24% (from 137 mg/dL to 104 mg/dL) by day 14, but this was not statistically significant. There was no significant difference in HDL cholesterol. The total/HDL level dropped from 4.54 (day 0) to 3.32 (day 14), and the LDL/HDL level dropped from 2.92 to 1.88; both results were highly significant (P <.001). Conclusion The rapid lipid reduction observed with atorvastatin may benefit the vascular endothelium. (Am Heart J 2000;140:249-52.)