The efficacy and tolerability of low doses of simvastatin (10 mg daily) were evaluated in a double-blind study conducted in 12 patients with moderate-grade familial hypercholesterolemia (baseline range of cholesterol levels, 240-290 mg/dl). Eight randomly selected subjects were administered active drug for eight consecutive weeks, and the other four were given placebo. At the end of treatment, the simvastatin-treated group showed a significant (P<0.001) decrease in total cholesterol (-26%), low-density-lipoprotein cholesterol (-35%), total cholesterol/high density lipoprotein cholesterol ratio (-25%), and apolipoprotein B levels (-31%). Significant changes in other lipid parameters were not observed, nor were adverse reactions or alterations in safety parameters recorded. In the placebo group, no changes were registered in any of the parameters. Simvastatin, at 10 mg daily, is able to almost normalize cholesterol levels in patients with light- to moderate-grade familial hypercholesterolemia, and considerably attenuate their atherogenic risk.