This study is an attempt to assess the possible effect of 4 different gene polymorphisms on patient's response to streptokinase after acute myocardial infarction. To achieve this goal, we studied 63 patients with acute anterior myocardial infarction (mean age: 54.3 ± 9.72 years, range: 34-76 years), Besides clinical relief of chest pain, patients' response to thrombolytic therapy was evaluated using ST-segment elevation both on admission and 2 hours following SK administration. We used the ST-segment resolution for assessment of response. Fifty percent STR was considered as a sign of effective reperfusion. For each patient DNA was extracted from a peripheral blood sample. For each gene polymorphism we used the specific primers for Restriction fragment length polymorphism (RFLP)-technique: Polymerase chain reaction (PCR) followed by the specific restriction enzyme. Out of the 63 pts studied for ACE insertion/deletion genotyping, fifty percent STR was most frequently observed in 100% of pts carrying I/I genotype, compared to 60% of heterozygous I/D genotype carriers and 66.7 of homozygous D/D carriers. The same pts (63 pts) were also assessed for PAI-1 genotyping, responders with 50% STR represented 66.7% of pts carrying 4G/4G genotype, 63.6% of 5G/5G pts, and 55% of the patients carrying 4G/5G. Platelet α2 receptor genotypes in 57 of the pts were assessed; the carriers of genotype 2 had the best response in terms of 50% STR (71.4% of patients compared to 58.3 and 50% of pts with genotype 1 and 3 respectively). Out of the 30 pts assessed for fibrinogen- β Bcl I, responders comprised 68.8 and 62.5% for B1 and B2 genotypes respectively. Pharmacogenetics aims at understanding how genetic variation contributes to variations in response to drugs. These polymorphisms that are involved in the pathophysiology of CAD can account for the variable response detected in different AMI patients receiving streptokinase.