DISCUSSION: HMG-CoA reductase inhibitors are popular lipid lowering agents. The most common adverse drug reaction is a transient chemical hepatitis of little clinical significance. Clinically significant rhabdomyolysis is extremely rare with an incidence of < 0.5%. HMG-CoA reductase inhibitors require metabolism by P-450 enzymes before they become active. Inhibition of the P-450 system leads to decreased metabolism of the statin drugs and higher plasma levels. The resultant increased delivery of the HMG-CoA reductase inhibitors to muscle cells decreases the production of cholesterol and cytochrome Q10 and makes muscles susceptible to oxidative damage and rhabdomyolysis. Cerivastatin is a third-generation HMG-CoA reductase inhibitor that is marketed as a``safer'' drug because it is metabolized by two different P-450 isoenzymes, CYP3A4 and 2C8. Cases of rhabdomyolysis in patients treated with cerivastatin and gemfibrozil have been reported; however, there have been no published reports of cerivastatin alone causing rhabdomyolysis. The etiology of rhabdomyolysis in this patient is somewhat puzzling. He was on no potent inhibitors of CYP3A4 nor did he have pre-existing hepatic or renal dysfunction. It may be that he had an intrinsic deficiency of CYP2C8. The treatment of HMG-CoA reductase inhibitor induced rhabdomyolysis involves withdrawal of the drug and supportive care. The myositis usually resolves completely although renal failure has been reported.