Although neovascularization has been noted in atherosclerotic plaque, the presence of neovascularization has not been correlated with clinical syndromes. This study examined the relation between neovascularization in atherosclerotic plaque removed during directional coronary atherectomy and clinical status in 28 patients. Neovascularization was determined by immunohistochemistry with endothelial cell-specific monoclonal antibodies and was found in nine (50%) of 18 specimens from patients with unstable angina and in only one (10%) of 10 specimens from patients with stable angina (p < 0.05). There was no significant relation between neovascularization and other clinical factors (age, sex, race, hypertension, diabetes, tobacco use, hypercholesterolemia, positive family history of coronary artery disease, history of myocardial infarction, or stenosis severity). These results suggest that neovoscularization may play a role in the pathogenesis of unstable angina.