A common mutation in coagulation factor V gene gives rise to factor V Leiden, which is resistant to the proteolytic activity of activated protein C. This mutation is known to be a major inherited risk factor for venous thrombosis. In order to investigate the possible pathogenetic role of factor V Leiden in coronary thrombosis, we screened patients with acute ischemic heart disease for this genetic mutation. We conducted a case-control study on 114 unrelated patients referred to the Cardiology Department of a University Hospital for coronary angiography. Fifty-three case patients with myocardial infarction or unstable angina were compared with 61 control patients seen for a different coronary syndrome or for stable angina pectoris. The two groups did not differ with respect to the well established risk factors for ischemic heart disease. For each patient genomic DNA was extracted from whole blood by standard techniques; the DNA region carrying the mutation was amplified by polymerase chain reaction, and the allele-specific restriction digestion was used in order to detect the mutation itself. The frequency of factor V Leiden was 0.028 among cases and 0.008 among controls (p = 0.5). According to the data presented, factor V Leiden cannot be considered as a risk factor for acute coronary events.