3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors decrease mevalonate and subsequently cholesterol synthesis competitively. Mevalonate is also the precursor of ubiquinone. Ubiquinone is an important component of electron transport chain. We therefore investigated the effect of simvastatin on rat blood and tissue ATP concentrations and the lipid composition of red blood cell membranes after 4 weeks of therapy. Significant reductions in rat plasma cholesterol, triglyceride, and blood ATP concentrations were detected. Tissue ATP levels were not affected. Membrane phospholipids increased, while cholesterol and the cholesterol to phospholipid ratio decreased (P < 0.05). A positive correlation between the plasma cholesterol concentration and the cholesterol to phospholipid ratio was noted (P < 0.05, r = 0.851). Our results show that HMG-CoA reductase inhibitors change the composition and probably also the functions of cell membrane lipids and blood ATP concentration.