HMG-CoA reductase inhibitors effectively reduce cholesterol levels, and this is associated with a lower rate of cardiovascular events. Some HMG-CoA reductase inhibitors are more effective than others in reducing low density lipoprotein (LDL) cholesterol, and such drugs should help patients achieve LDL cholesterol targets prescribed by the National Cholesterol Education Panel (NCEP). This paper describes the design of a trial comparing the clinical efficacy and cost effectiveness of four HMG-CoA reductase inhibitors in reducing LDL cholesterol to specified targets. This trial is being conducted in 30 physicians' practices in the USA. Its primary aim is to assess the resource use required to achieve and maintain NCEP targets by all patients randomised and followed up for one year.