Although this study is the first to show an interaction between ACE I/D genotypes and the response of plasma lipids to therapy, interactions between genetic polymorphisms and drug efficacy have been recognized for many years (28). The classic example is that of cytochrome P450 isozymes, which determine interindividual variations in the metabolism of many drugs in the liver, including the HMG-CoA reductase inhibitors (28). With regard to lipids metabolism, polymorphisms in genes coding for apo B, apo A1/CIII and apo E have been shown to influence the response of plasma lipids to treatment with gemfibrozil (29) and probucol (30), respectively. Similarly, polymorphisms in the genes coding for cholesteryl ester transfer protein, apo E, apo A-1, apo A-IV have been associated with response of plasma lipids to dietary interventions (5- 6,31). Other examples of gene-treatment interaction include polymorphisms in the neurotransmitter sertonin type IIA receptor and alpha-adducin genes which are associated with the clinical response to antipsychotic drugs in schizophrenic patients (32) and to diuretics in hypertensive patients (33), respectively. Thus, genetic polymorphisms, in part, form the basis for interindividual variations in the response to drug therapy.