The effects of atorvastatin on levels of the CD40 ligand (CD40L or CD154) and P-selectin on platelets were investigated in patients with hypercholesterolemia. The major finding was that short-term atorvastatin treatment (8 weeks) in a group of hypercholesterolemic patients resulted in significant suppression of CD40L and P-selectin expression. Moreover, there was a significant correlation between the magnitude of CD40L downregulation and that of very low-density lipoprotein cholesterol, the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol, and triglycerides. In hypercholesterolemic patients, in addition to its effects on decreasing cholesterol, atorvastatin can intervene in the interaction of CD40-CD40L and the expression of P-selectin on platelets. Thus, interference of CD40-CD40L can be recognized as an integral part of the anti-inflammatory activity of atorvastatin in hypercholesterolemia.